Richard B. Hayes, D.D.S., Ph.D., M.P.H.

Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium
Chuang, Shu-Chun; Jenab, Mazda; Heck, Julia E; Bosetti, Cristina; Talamini, Renato; Matsuo, Keitaro; Castellsague, Xavier; Franceschi, Silvia; Herrero, Rolando; Winn, Deborah M; La Vecchia, Carlo; Morgenstern, Hal; Zhang, Zuo-Feng; Levi, Fabio; Maso, Luigino Dal; Kelsey, Karl; McClean, Michael D; Vaughan, Thomas; Lazarus, Philip; Muscat, Joshua; Ramroth, Heribert; Chen, Chu; Schwartz, Stephen M; Eluf-Neto, Jose; Hayes, Richard B; Purdue, Mark; Boccia, Stefania; Cadoni, Gabriella; Zaridze, David; Koifman, Sergio; Curado, Maria Paula; Ahrens, Wolfgang; Benhamou, Simone; Matos, Elena; Lagiou, Pagona; Szeszenia-Dabrowska, Neonilla; Olshan, Andrew F; Fernandez, Leticia; Menezes, Ana; Agudo, Antonio; Daudt, Alexander W; Merletti, Franco; Macfarlane, Gary J; Kjaerheim, Kristina; Mates, Dana; Holcatova, Ivana; Schantz, Stimson; Yu, Guo-Pei; Simonato, Lorenzo; Brenner, Hermann; Mueller, Heiko; Conway, David I; Thomson, Peter; Fabianova, Eleonora; Znaor, Ariana; Rudnai, Peter; Healy, Claire M; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia
2012 Jan;23(1):69-88, Cancer causes & control. ccc
We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97)
— id: 149788, year: 2012, vol: 23, page: 69, stat: Journal Article,

Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence
Ahn, Jiyoung; Kibel, Adam S; Park, Jong Y; Rebbeck, Timothy R; Rennert, Hanna; Stanford, Janet L; Ostrander, Elaine A; Chanock, Stephen; Wang, Ming-Hsi; Mittal, Rama D; Isaacs, William B; Platz, Elizabeth A; Hayes, Richard B
2011 Mar 1;17(5):1075-1081, Clinical cancer research
PURPOSE: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain. EXPERIMENTAL DESIGN: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights. RESULTS: MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence. CONCLUSIONS: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants
— id: 130909, year: 2011, vol: 17, page: 1075, stat: Journal Article,

Oral Microbiome Profiles: 16S rRNA Pyrosequencing and Microarray Assay Comparison
Ahn, Jiyoung; Yang, Liying; Paster, Bruce J; Ganly, Ian; Morris, Luc; Pei, Zhiheng; Hayes, Richard B
2011 ;6(7):e22788-e22788, PLoS ONE
OBJECTIVES: The human oral microbiome is potentially related to diverse health conditions and high-throughput technology provides the possibility of surveying microbial community structure at high resolution. We compared two oral microbiome survey methods: broad-based microbiome identification by 16S rRNA gene sequencing and targeted characterization of microbes by custom DNA microarray. METHODS: Oral wash samples were collected from 20 individuals at Memorial Sloan-Kettering Cancer Center. 16S rRNA gene survey was performed by 454 pyrosequencing of the V3-V5 region (450 bp). Targeted identification by DNA microarray was carried out with the Human Oral Microbe Identification Microarray (HOMIM). Correlations and relative abundance were compared at phylum and genus level, between 16S rRNA sequence read ratio and HOMIM hybridization intensity. RESULTS: The major phyla, Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria were identified with high correlation by the two methods (r = 0.70 approximately 0.86). 16S rRNA gene pyrosequencing identified 77 genera and HOMIM identified 49, with 37 genera detected by both methods; more than 98% of classified bacteria were assigned in these 37 genera. Concordance by the two assays (presence/absence) and correlations were high for common genera (Streptococcus, Veillonella, Leptotrichia, Prevotella, and Haemophilus; Correlation = 0.70-0.84). CONCLUSION: Microbiome community profiles assessed by 16S rRNA pyrosequencing and HOMIM were highly correlated at the phylum level and, when comparing the more commonly detected taxa, also at the genus level. Both methods are currently suitable for high-throughput epidemiologic investigations relating identified and more common oral microbial taxa to disease risk; yet, pyrosequencing may provide a broader spectrum of taxa identification, a distinct sequence-read record, and greater detection sensitivity
— id: 136523, year: 2011, vol: 6, page: e22788, stat: Journal Article,

Global Levels of Histone Modifications in Peripheral Blood Mononuclear Cells of Subjects with Exposure to Nickel
Arita A; Niu J; Qu Q; Zhao N; Ruan Y; Nadas A; Chervona Y; Wu F; Sun H; Hayes RB; Costa M
2011 Oct 24;:198-203 #, Environmental health perspectives
Background: Occupational exposure to nickel is associated with an increased risk for lung and nasal cancers. Nickel compounds exhibit weak mutagenic activity, cause gene amplification, and disrupt cellular epigenetic homeostasis. However, the nickel-induced changes in global histone modification levels have only been tested in vitro. Objective: This study was conducted in a Chinese population to determine whether occupational exposure to nickel is associated with alterations of global histone modification levels and to evaluate the inter-and intra-individual variance of global histone modification levels. Method: 45 subjects with occupational exposure to nickel and 75 referents were recruited. Urinary nickel and global H3K4 trimethylation (H3K4me3), H3K9 acetylation (H3K9ac), and H3K9 dimethylation (H3K9me2) levels were measured in peripheral blood mononuclear cells (PBMCs) of subjects. Results: H3K4me3 was elevated (0.25%+/-0.11%, 0.15%+/-0.04%, p=0.0004) and H3K9me2 was decreased (0.11%+/-0.05%, 0.15%+/-0.04%, p=0.003) in Ni-exposed subjects. H3K4me3 was positively (r=0.4, p=0.0008) and H3K9ac was negatively (r=0.1, p=0.01) associated with urinary nickel. Inter-individual variances of H3K4me3, H3K9ac, and H3K9me2 were larger relative to intra-individual variance in both groups, resulting in reliability coefficients, estimate of consistency of a set of measurements, of 0.75, 0.74, and 0.97 for H3K4me3, H3K9ac, and H3K9me2, respectively, for referent subjects. Reliability coefficients of 0.60, 0.67, and 0.79 were found for H3K4me3, H3K9ac, and H3K9me2, respectively, for Ni-exposed subjects. Conclusion: The results of this study indicate that occupational exposure to nickel is associated with alterations of global histone modification levels and that measurements of global levels of histone modifications are relatively stable over time in human PBMCs
— id: 141421, year: 2011, vol: , page: 198, stat: Journal Article,

Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the breast and prostate cancer cohort consortium (BPC3)
Beckmann, L; Husing, A; Setiawan, V W; Amiano, P; Clavel-Chapelon, F; Chanock, S J; Cox, D G; Diver, R; Dossus, L; Feigelson, H S; Haiman, C; Hallmans, G; Hayes, R B; Henderson, B E; Hoover, R N; Hunter, D J; Khaw, K; Kolonel, L N; Kraft, P; Lund, E; Le Marchand, L; Peeters, P H M; Riboli, E; Stram, D; Thomas, G; Thun, M J; Tumino, R; Trichopoulos, D; Vogel, U; Willett, W C; Yeager, M; Ziegler, R; Hankinson, S E; Kaaks, R
2011 Feb;96(2):E360-E367, Journal of clinical endocrinology & metabolism
CONTEXT: Sex steroids play a central role in breast cancer development. OBJECTIVE: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG. DESIGN: Data on 700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC). SETTING AND PARTICIPANTS: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC. MAIN OUTCOME MEASURES: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk. RESULTS: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk. CONCLUSIONS: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS
— id: 134163, year: 2011, vol: 96, page: E360, stat: Journal Article,

Large-scale fine mapping of the HNF1B locus and prostate cancer risk
Berndt, Sonja I; Sampson, Joshua; Yeager, Meredith; Jacobs, Kevin B; Wang, Zhaoming; Hutchinson, Amy; Chung, Charles; Orr, Nick; Wacholder, Sholom; Chatterjee, Nilanjan; Yu, Kai; Kraft, Peter; Feigelson, Heather Spencer; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Haiman, Christopher; Henderson, Brian; Kolonel, Laurence; Le Marchand, Loic; Siddiq, Afshan; Riboli, Elio; Travis, Ruth C; Kaaks, Rudolf; Isaacs, William; Isaacs, Sarah; Wiley, Kathleen E; Gronberg, Henrik; Wiklund, Fredrik; Stattin, Par; Xu, Jianfeng; Zheng, S Lilly; Sun, Jielin; Vatten, Lars J; Hveem, Kristian; Njolstad, Inger; Gerhard, Daniela S; Tucker, Margaret; Hayes, Richard B; Hoover, Robert N; Fraumeni, Joseph F Jr; Hunter, David J; Thomas, Gilles; Chanock, Stephen J
2011 Aug 15;20(16):3322-3329, Human molecular genetics
Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 x 10(-8) with the most significant association with rs4430796 (P = 1.62 x 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2)= 0.64), rs7405696 was also associated with risk (P = 9.35 x 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 x 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 x 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer
— id: 135593, year: 2011, vol: 20, page: 3322, stat: Journal Article,

A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers
Chen, Dan; Truong, Therese; Gaborieau, Valerie; Byrnes, Graham; Chabrier, Amelie; Chuang, Shu-chun; Olshan, Andrew F; Weissler, Mark C; Luo, Jingchun; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Franceschi, Silvia; Herrero, Rolando; Talamini, Renato; Kelsey, Karl T; Christensen, Brock; McClean, Michael D; Lacko, Martin; Manni, Johannes J; Peters, Wilbert H M; Lubinski, Jan; Trubicka, Joanna; Lener, Marcin; Muscat, Joshua E; Lazarus, Philip; Wei, Qingyi; Sturgis, Erich M; Zhang, Zuo-Feng; Chang, Shen-Chih; Wang, Renyi; Schwartz, Stephen M; Chen, Chu; Benhamou, Simone; Lagiou, Pagona; Holcatova, Ivana; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana V; Barzan, Luigi; Canova, Cristina; Thakker, Nalin S; Conway, David I; Znaor, Ariana; Healy, Claire M; Ahrens, Wolfgang; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wunsch-Filho, Victor; Eluf-Neto, Jose; Fernandez, Leticia; Boccia, Stefania; Hashibe, Mia; Hayes, Richard B; Boffetta, Paolo; Brennan, Paul; McKay, James D
2011 Apr;20(4):658-664, Cancer epidemiology biomarkers & prevention
BACKGROUND: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). METHODS: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies. RESULTS: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 x 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 x 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86). CONCLUSIONS: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. IMPACT: Further research is warranted to elucidate the mechanisms underlying these observations
— id: 134231, year: 2011, vol: 20, page: 658, stat: Journal Article,

Fine mapping of a region of chromosome 11q13 reveals multiple independent loci associated with risk of prostate cancer
Chung, Charles C; Ciampa, Julia; Yeager, Meredith; Jacobs, Kevin B; Berndt, Sonja I; Hayes, Richard B; Gonzalez-Bosquet, Jesus; Kraft, Peter; Wacholder, Sholom; Orr, Nick; Yu, Kai; Hutchinson, Amy; Boland, Joseph; Chen, Quan; Feigelson, Heather Spencer; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Haiman, Christopher A; Henderson, Brian E; Kolonel, Laurence; Le Marchand, Loic; Siddiq, Afshan; Riboli, Elio; Key, Tim J; Kaaks, Rudolf; Isaacs, William B; Isaacs, Sarah D; Gronberg, Henrik; Wiklund, Fredrik; Xu, Jianfeng; Vatten, Lars J; Hveem, Kristian; Njolstad, Inger; Gerhard, Daniela S; Tucker, Margaret; Hoover, Robert N; Fraumeni, Joseph F Jr; Hunter, David J; Thomas, Gilles; Chatterjee, Nilanjan; Chanock, Stephen J
2011 Jul 15;20(14):2869-2878, Human molecular genetics
Genome-wide association studies have identified prostate cancer susceptibility alleles on chromosome 11q13. As part of the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, the region flanking the most significant marker, rs10896449, was fine mapped in 10 272 cases and 9123 controls of European origin (10 studies) using 120 common single nucleotide polymorphisms (SNPs) selected by a two-staged tagging strategy using HapMap SNPs. Single-locus analysis identified 18 SNPs below genome-wide significance (P< 10(-8)) with rs10896449 the most significant (P= 7.94 x 10(-19)). Multi-locus models that included significant SNPs sequentially identified a second association at rs12793759 [odds ratio (OR) = 1.14, P= 4.76 x 10(-5), adjusted P= 0.004] that is independent of rs10896449 and remained significant after adjustment for multiple testing within the region. rs10896438, a proxy of previously reported rs12418451 (r(2)= 0.96), independent of both rs10896449 and rs12793759 was detected (OR = 1.07, P= 5.92 x 10(-3), adjusted P= 0.054). Our observation of a recombination hotspot that separates rs10896438 from rs10896449 and rs12793759, and low linkage disequilibrium (rs10896449-rs12793759, r(2)= 0.17; rs10896449-rs10896438, r(2)= 0.10; rs12793759-rs10896438, r(2)= 0.12) corroborate our finding of three independent signals. By analysis of tagged SNPs across approximately 123 kb using next generation sequencing of 63 controls of European origin, 1000 Genome and HapMap data, we observed multiple surrogates for the three independent signals marked by rs10896449 (n= 31), rs10896438 (n= 24) and rs12793759 (n= 8). Our results indicate that a complex architecture underlying the common variants contributing to prostate cancer risk at 11q13. We estimate that at least 63 common variants should be considered in future studies designed to investigate the biological basis of the multiple association signals
— id: 135269, year: 2011, vol: 20, page: 2869, stat: Journal Article,

Genetic contributions to the association between adult height and testicular germ cell tumors
Cook, Michael B; Chia, Victoria M; Berndt, Sonja I; Graubard, Barry I; Chanock, Stephen J; Rubertone, Mark V; Erickson, Ralph L; Hayes, Richard B; McGlynn, Katherine A
2011 Jun;40(3):731-739, International journal of epidemiology
BACKGROUND: Previously, we have shown that increasing adult height is associated with increased risk of testicular germ-cell tumor (TGCT). Recently, a number of single nucleotide polymorphisms (SNPs) have been found to be related to height. We examined whether these SNPs were associated with TGCT and whether they explained the relationship between height and TGCT. METHODS: We genotyped 15 height-related SNPs in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study. DNA was extracted from buccal cell samples and Taqman assays were used to type the selected SNPs. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: There were 561 cases and 676 controls for analysis. Two SNPs were found to be associated with risk of TGCT, rs6060373 (CC vs TT, OR = 1.51, 95% CI: 1.06-2.15) and rs143384 (CC vs TT, OR = 1.53, 95% CI: 1.09-2.15). rs6060373 is an intronic polymorphism of ubiquinol-cytochrome c reductase complex chaperone (UQCC), and rs143384 is a 5'UTR polymorphism of growth differentiation factor 5 (GDF5). No individual SNP attenuated the association between height and TGCT. Adjustment for all SNPs previously associated with adult height reduced the associations between adult height and TGCT by ~8.5%, although the P-value indicated only weak evidence that this difference was important (P = 0.26). CONCLUSIONS: This novel analysis provides tentative evidence that SNPs which are associated with adult height may also share an association with risk of TGCT
— id: 139033, year: 2011, vol: 40, page: 731, stat: Journal Article,

Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial
Cross, Amanda J; Sinha, Rashmi; Wood, Richard J; Xue, Xiaonan; Huang, Wen-Yi; Yeager, Meredith; Hayes, Richard B; Gunter, Marc J
2011 Sep;4(9):1465-1475, Cancer prevention research (Philadelphia, Pa.)
Red meat consumption has been positively associated with colorectal cancer; however, the biological mechanism underlying this relationship is not understood. Red meat is a major source of iron, which may play a role in colorectal carcinogenesis via increased crypt cell proliferation, cytotoxicity, and endogenous N-nitrosation. In a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we prospectively evaluated multiple iron exposure parameters, including dietary intake and serum measures of iron, ferritin, transferrin, total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) in relation to incident colorectal adenoma in 356 cases and 396 matched polyp-free controls. We also investigated variation in eight key genes involved in iron homeostasis in relation to colorectal adenoma in an additional series totaling 1,126 cases and 1,173 matched controls. We observed a positive association between red meat intake and colorectal adenoma [OR comparing extreme quartiles (OR(q4-q1)) = 1.59, 95% CI = 1.02-2.49, P(trend) = 0.03]. Serum TIBC and UIBC were inversely associated with colorectal adenoma (OR(q4-q1) = 0.57, 95% CI = 0.37-0.88, P(trend) = 0.03; and OR(q4-q1) = 0.62, 95% CI = 0.40-0.95, P(trend) = 0.04, respectively). Colorectal adenoma was not associated with serum ferritin, iron, or transferrin saturation or with polymorphisms in genes involved in iron homeostasis. Serum TIBC and UIBC, parameters that have a reciprocal relationship with overall iron load, were inversely related to colorectal adenoma, suggesting that individuals with lower iron status have a reduced risk of developing colorectal adenoma
— id: 139037, year: 2011, vol: 4, page: 1465, stat: Journal Article,

Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis
Daugherty, Sarah E; Pfeiffer, Ruth M; Sigurdson, Alice J; Hayes, Richard B; Leitzmann, Michael; Schatzkin, Arthur; Hollenbeck, Albert R; Silverman, Debra T
2011 Apr 1;173(7):721-730, American journal of epidemiology
Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers
— id: 134248, year: 2011, vol: 173, page: 721, stat: Journal Article,

DNA repair gene polymorphisms and tobacco smoking in the risk for colorectal adenomas
Gao, Ying; Hayes, Richard B; Huang, Wen-Yi; Caporaso, Neil E; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen J; Berndt, Sonja I
2011 Jun;32(6):882-887, Carcinogenesis
DNA damage is thought to play a critical role in the development of colorectal adenoma. Variation in DNA repair genes may alter their capacity to correct endogenous and exogenous DNA damage. We explored the association between common single-nucleotide polymorphisms (SNPs) in DNA repair genes and adenoma risk with a case-control study nested in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 1338 left sided, advanced colorectal adenoma cases and 1503 matched controls free of left-sided polyps were included in the study. Using DNA extracted from blood, 3144 tag SNPs in 149 DNA repair genes were successfully genotyped. Among Caucasians, 30 SNPs were associated with adenoma risk at P < 0.01, with four SNPs remaining significant after gene-based adjustment for multiple testing. The most significant finding was for a non-synonymous SNP (rs9350) in Exonuclease-1 (EXO1) [odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.11-1.51, P = 0.001)], which was predicted to be damaging using bioinformatics methods. However, the association was limited to smokers with a strong risk for current smokers (OR = 2.15, 95% CI = 1.27-3.65) and an intermediate risk for former smokers (OR = 1.45, 95% CI = 1.14-1.82) and no association for never smokers (OR = 0.98, 95% CI = 0.76-1.25) (P(interaction) = 0.002). Among the top findings, an SNP (rs17503908) in ataxia telangiectasia mutated (ATM) was inversely related to adenoma risk (OR = 0.75, 95% CI = 0.63-0.91). The association was restricted to never smokers (OR = 0.55, 95% CI = 0.40-0.76) with no increased risk observed among smokers (OR = 0.89, 95% CI = 0.70-1.13) (P(interaction) = 0.006). This large comprehensive study, which evaluated all presently known DNA repair genes, suggests that polymorphisms in EXO1 and ATM may be associated with risk for advanced colorectal adenoma with the associations modified by tobacco-smoking status
— id: 139035, year: 2011, vol: 32, page: 882, stat: Journal Article,

A prospective evaluation of C-reactive protein levels and colorectal adenoma development
Gunter, Marc J; Cross, Amanda J; Huang, Wen-Yi; Stanczyk, Frank Z; Purdue, Mark; Xue, Xiaonan; Schoen, Robert; Limburg, Paul J; Schatzkin, Arthur; Sinha, Rashmi; Hayes, Richard B
2011 Mar;20(3):537-544, Cancer epidemiology biomarkers & prevention
BACKGROUND: Inflammation is hypothesized to play a role in colorectal tumorigenesis. Circulating levels of C-reactive protein (CRP), a serologic marker of the inflammatory response, have been positively associated with colorectal cancer development in some studies; however, there are limited data on the relation of CRP with colorectal adenomas, established precursors of colorectal cancer. METHODS: A nested case-control investigation of CRP levels and incident colorectal adenoma was conducted in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized trial of 154,942 individuals designed to test the efficacy of flexible sigmoidoscopy on colorectal cancer mortality when performed once, and then repeated 3 to 5 years later. Serum CRP levels were measured in baseline blood specimens from participants who were free of polyps in the left-sided colorectum at the baseline screening procedure, but who were found at the subsequent screen to have at least one colorectal adenoma (n=356), and in a set of polyp-free, frequency-matched controls (n=396). RESULTS: In a multivariable logistic regression model that included established colorectal adenoma risk factors, a 1-unit increase in log CRP level was associated with a 15% reduction in risk of developing colorectal adenoma (OR=0.85, 95% CI, 0.75-0.98, Ptrend=0.01). This association did not differ according to body size, smoking behavior, gender, use of nonsteroidal antiinflammatory drugs, or adenoma location. CONCLUSIONS: High circulating CRP levels may be protective against colorectal adenoma development. IMPACT: Though at contrast with mechanistic data on inflammation and colorectal tumorigenesis, this finding is not inconsistent with prior results on CRP and colorectal adenoma and warrants further investigation
— id: 139032, year: 2011, vol: 20, page: 537, stat: Journal Article,

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21
Haiman, Christopher A; Chen, Gary K; Blot, William J; Strom, Sara S; Berndt, Sonja I; Kittles, Rick A; Rybicki, Benjamin A; Isaacs, William B; Ingles, Sue A; Stanford, Janet L; Diver, W Ryan; Witte, John S; Hsing, Ann W; Nemesure, Barbara; Rebbeck, Timothy R; Cooney, Kathleen A; Xu, Jianfeng; Kibel, Adam S; Hu, Jennifer J; John, Esther M; Gueye, Serigne M; Watya, Stephen; Signorello, Lisa B; Hayes, Richard B; Wang, Zhaoming; Yeboah, Edward; Tettey, Yao; Cai, Qiuyin; Kolb, Suzanne; Ostrander, Elaine A; Zeigler-Johnson, Charnita; Yamamura, Yuko; Neslund-Dudas, Christine; Haslag-Minoff, Jennifer; Wu, William; Thomas, Venetta; Allen, Glenn O; Murphy, Adam; Chang, Bao-Li; Zheng, S Lilly; Leske, M Cristina; Wu, Suh-Yuh; Ray, Anna M; Hennis, Anselm J M; Thun, Michael J; Carpten, John; Casey, Graham; Carter, Erin N; Duarte, Edder R; Xia, Lucy Y; Sheng, Xin; Wan, Peggy; Pooler, Loreall C; Cheng, Iona; Monroe, Kristine R; Schumacher, Fredrick; Le Marchand, Loic; Kolonel, Laurence N; Chanock, Stephen J; Berg, David Van Den; Stram, Daniel O; Henderson, Brian E
2011 Jun;43(6):570-573, Nature genetics
In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 x 10(-13)). The frequency of the risk allele is approximately 5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations
— id: 134178, year: 2011, vol: 43, page: 570, stat: Journal Article,

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study
Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G; Severi, Gianluca; Schleutker, Johanna; Weischer, Maren; Campa, Daniele; Riboli, Elio; Key, Tim; Gronberg, Henrik; Hunter, David J; Kraft, Peter; Thun, Michael J; Ingles, Sue; Chanock, Stephen; Albanes, Demetrius; Hayes, Richard B; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Pharoah, Paul; Schumacher, Fredrick; Henderson, Brian E; Stanford, Janet L; Ostrander, Elaine A; Sorensen, Karina Dalsgaard; Dork, Thilo; Andriole, Gerald; Dickinson, Joanne L; Cybulski, Cezary; Lubinski, Jan; Spurdle, Amanda; Clements, Judith A; Chambers, Suzanne; Aitken, Joanne; Gardiner, R A Frank; Thibodeau, Stephen N; Schaid, Dan; John, Esther M; Maier, Christiane; Vogel, Walther; Cooney, Kathleen A; Park, Jong Y; Cannon-Albright, Lisa; Brenner, Hermann; Habuchi, Tomonori; Zhang, Hong-Wei; Lu, Yong-Jie; Kaneva, Radka; Muir, Ken; Benlloch, Sara; Leongamornlert, Daniel A; Saunders, Edward J; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Guy, Michelle; O'Brien, Lynne T; Wilkinson, Rosemary A; Hall, Amanda L; Sawyer, Emma J; Dadaev, Tokhir; Morrison, Jonathan; Dearnaley, David P; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Van As, Nicholas; Woodhouse, Christopher J; Thompson, Alan; Christmas, Tim; Ogden, Chris; Cooper, Colin S; Lophatonanon, Aritaya; Southey, Melissa C; Hopper, John L; English, Dallas R; Wahlfors, Tiina; Tammela, Teuvo L J; Klarskov, Peter; Nordestgaard, Borge G; Roder, M Andreas; Tybjaerg-Hansen, Anne; Bojesen, Stig E; Travis, Ruth; Canzian, Federico; Kaaks, Rudolf; Wiklund, Fredrik; Aly, Markus; Lindstrom, Sara; Diver, W Ryan; Gapstur, Susan; Stern, Mariana C; Corral, Roman; Virtamo, Jarmo; Cox, Angela; Haiman, Christopher A; Le Marchand, Loic; Fitzgerald, Liesel; Kolb, Suzanne; Kwon, Erika M; Karyadi, Danielle M; Orntoft, Torben Falck; Borre, Michael; Meyer, Andreas; Serth, Jurgen; Yeager, Meredith; Berndt, Sonja I; Marthick, James R; Patterson, Briony; Wokolorczyk, Dominika; Batra, Jyotsna; Lose, Felicity; McDonnell, Shannon K; Joshi, Amit D; Shahabi, Ahva; Rinckleb, Antje E; Ray, Ana; Sellers, Thomas A; Lin, Hui-Yi; Stephenson, Robert A; Farnham, James; Muller, Heiko; Rothenbacher, Dietrich; Tsuchiya, Norihiko; Narita, Shintaro; Cao, Guang-Wen; Slavov, Chavdar; Mitev, Vanio; Easton, Douglas F; Eeles, Rosalind A
2011 Aug;43(8):785-791, Nature genetics
Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 x 10(-8) to P = 2.7 x 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining approximately 25% of the familial risk in this disease, have now been identified
— id: 138440, year: 2011, vol: 43, page: 785, stat: Journal Article,

Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3
Lindstrom, Sara; Schumacher, Fredrick; Siddiq, Afshan; Travis, Ruth C; Campa, Daniele; Berndt, Sonja I; Diver, W Ryan; Severi, Gianluca; Allen, Naomi; Andriole, Gerald; Bueno-de-Mesquita, Bas; Chanock, Stephen J; Crawford, David; Gaziano, J Michael; Giles, Graham G; Giovannucci, Edward; Guo, Carolyn; Haiman, Christopher A; Hayes, Richard B; Halkjaer, Jytte; Hunter, David J; Johansson, Mattias; Kaaks, Rudolf; Kolonel, Laurence N; Navarro, Carmen; Riboli, Elio; Sacerdote, Carlotta; Stampfer, Meir; Stram, Daniel O; Thun, Michael J; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J; Yeager, Meredith; Henderson, Brian; Ma, Jing; Le Marchand, Loic; Albanes, Demetrius; Kraft, Peter
2011 ;6(2):e17142-e17142, PLoS ONE
Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade) and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10(2)). Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test), where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade < 8) tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined
— id: 133436, year: 2011, vol: 6, page: e17142, stat: Journal Article,

An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies
Lubin, Jay H; Muscat, Joshua; Gaudet, Mia M; Olshan, Andrew F; Curado, Maria Paula; Dal Maso, Luigino; Wunsch-Filho, Victor; Sturgis, Erich M; Szeszenia-Dabrowska, Neonilia; Castellsague, Xavier; Zhang, Zuo-Feng; Smith, Elaine; Fernandez, Leticia; Matos, Elena; Franceschi, Silvia; Fabianova, Eleonora; Rudnai, Peter; Purdue, Mark P; Mates, Dana; Wei, Qingyi; Herrero, Rolando; Kelsey, Karl; Morgenstern, Hal; Shangina, Oxana; Koifman, Sergio; Lissowska, Jolanta; Levi, Fabio; Daudt, Alexander W; Neto, Jose Eluf; Chen, Chu; Lazarus, Philip; Winn, Deborah M; Schwartz, Stephen M; Boffetta, Paolo; Brennan, Paul; Menezes, Ana; La Vecchia, Carlo; McClean, Michael; Talamini, Renato; Rajkumar, Thangarajan; Hayes, Richard B; Hashibe, Mia
2011 Sep;22(9):1217-1231, Cancer causes & control. ccc
BACKGROUND: Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors. METHODS: We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models. RESULTS: ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (>/= 25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers. CONCLUSIONS: The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified
— id: 139038, year: 2011, vol: 22, page: 1217, stat: Journal Article,

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium
McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Holcatova, Ivana; Janout, Vladimir; Foretova, Lenka; Lagiou, Pagona; Trichopoulos, Dimitrios; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Kjaerheim, Kristina; Macfarlane, Gary J; Macfarlane, Tatiana V; Simonato, Lorenzo; Canova, Cristina; Agudo, Antonio; Castellsague, Xavier; Lowry, Ray; Conway, David I; McKinney, Patricia A; Healy, Claire M; Toner, Mary E; Znaor, Ariana; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wunsch-Filho, Victor; Neto, Jose Eluf; Garrote, Leticia Fernandez; Boccia, Stefania; Cadoni, Gabriella; Arzani, Dario; Olshan, Andrew F; Weissler, Mark C; Funkhouser, William K; Luo, Jingchun; Lubinski, Jan; Trubicka, Joanna; Lener, Marcin; Oszutowska, Dorota; Schwartz, Stephen M; Chen, Chu; Fish, Sherianne; Doody, David R; Muscat, Joshua E; Lazarus, Philip; Gallagher, Carla J; Chang, Shen-Chih; Zhang, Zuo-Feng; Wei, Qingyi; Sturgis, Erich M; Wang, Li-E; Franceschi, Silvia; Herrero, Rolando; Kelsey, Karl T; McClean, Michael D; Marsit, Carmen J; Nelson, Heather H; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Zhong, Shilong; Lacko, Martin; Manni, Johannes J; Peters, Wilbert H M; Hung, Rayjean J; McLaughlin, John; Vatten, Lars; Njolstad, Inger; Goodman, Gary E; Field, John K; Liloglou, Triantafillos; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Gonzalez, Carlos A; Quiros, J Ramon; Martinez, Carmen; Navarro, Carmen; Ardanaz, Eva; Larranaga, Nerea; Khaw, Kay-Tee; Key, Timothy; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Trichopoulou, Antonia; Linseisen, Jakob; Boeing, Heiner; Hallmans, Goran; Overvad, Kim; Tjonneland, Anne; Kumle, Merethe; Riboli, Elio; Valk, Kristjan; Vooder, Tonu; Metspalu, Andres; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Blanche, Helene; Gut, Ivo G; Galan, Pilar; Heath, Simon; Hashibe, Mia; Hayes, Richard B; Boffetta, Paolo; Lathrop, Mark; Brennan, Paul
2011 Mar;7(3):e1001333-e1001333, PLoS Genetics
Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p </= 5 x 10). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1x10) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 x 10) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10); rs1229984-ADH1B, p = 7 x 10; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility
— id: 138494, year: 2011, vol: 7, page: e1001333, stat: Journal Article,

The association between inflammation-related genes and serum androgen levels in men: The prostate, lung, colorectal, and ovarian study
Meyer TE; Chu LW; Li Q; Yu K; Rosenberg PS; Menashe I; Chokkalingam AP; Quraishi SM; Huang WY; Weiss JM; Kaaks R; Hayes RB; Chanock SJ; Hsing AW
2011 Jan;72(1):65-71 L, Prostate
BACKGROUND: Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes. METHODS: In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation-related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5alpha-androstane-3alpha, 17beta-diol glucuronide [3alphadiol G], and 4-androstene-3,17-dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome-wide scan. SNP-hormone associations were evaluated using linear regression of hormones adjusted for age. Gene-based P values were generated using an adaptive rank truncated product (ARTP) method. RESULTS: Suggestive associations were observed for two inflammation-related genes and circulating androgen levels (false discovery rate [FDR] q-value <0.1) in both SNP and gene-based tests. Specifically, T was associated with common variants in MMP2 and CD14, with the most significant SNPs being rs893226G > T in MMP2 and rs3822356T > C in CD14 (FDR q-value = 0.09 for both SNPs). Other genes implicated in either SNP or gene-based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione. CONCLUSION: These results suggest possible cross-talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk. Prostate (c) 2011 Wiley-Liss, Inc
— id: 139036, year: 2011, vol: 72, page: 65, stat: Journal Article,

Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer
Morris, Luc G T; Sikora, Andrew G; Hayes, Richard B; Patel, Snehal G; Ganly, Ian
2011 May;22(5):671-679, Cancer causes & control. ccc
BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) are at significantly elevated risk of second primary malignancies (SPM), most commonly within the head and neck, lung, and esophagus (HNLE). Our objectives were to quantify the excess risk of SPM across all anatomic sites in which SPM risk is meaningfully elevated, including non-HNLE sites, in a large cohort of US patients. METHODS: Population-based analysis of 75,087 patients with HNSCC in the SEER program, quantifying excess SPM risk by integrating relative (standardized incidence ratio; SIR) and absolute (excess absolute risk per 10,000 person-years at risk; EAR) statistics. RESULTS: In HNSCC patients, the SIR of a second primary solid cancer was 2.2 (95% CI 2.1-2.2), corresponding to EAR of 167.7 additional cases per 10,000 person-years at risk. Over 1 year, 60 patients would need to be followed to observe one excess SPM. Lung cancer burden was most markedly elevated in absolute terms (EAR = 75.2), followed by HN (EAR = 59.8), esophageal (EAR = 14.2), and colorectal (EAR = 4.3) cancers. Lesser but significant excess risks were also observed for cancers of the bladder, liver, stomach, pancreas, kidney, salivary glands, nasopharynx, uterine cervix, and lymphoma. CONCLUSIONS: Data from a large population-based US cohort reveals that HNSCC patients experience markedly excess risk of SPM, predominantly in the HNLE sites. Furthermore, the risk of SPM is also meaningfully elevated, although to a lesser degree, in multiple other tobacco-associated sites
— id: 134265, year: 2011, vol: 22, page: 671, stat: Journal Article,

Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer
Morris, Luc G T; Sikora, Andrew G; Patel, Snehal G; Hayes, Richard B; Ganly, Ian
2011 Feb 20;29(6):739-746, Journal of clinical oncology
PURPOSE: Patients with head and neck squamous cell carcinoma (HNSCC) are at elevated risk of second primary malignancies (SPM), most commonly of the head and neck (HN), lung, and esophagus. Our objectives were to identify HNSCC subsite-specific differences in SPM risk and distribution and to describe trends in risk over 3 decades, before and during the era of human papillomavirus (HPV) -associated oropharyngeal SCC. METHODS: Population-based cohort study of 75,087 patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER) program. SPM risk was quantified by using standardized incidence ratios (SIRs), excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear regression. RESULTS: In patients with HNSCC, the SIR of second primary solid tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR. The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per 10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR). The most common SPM site for patients with oral cavity and oropharynx SCC was HN; for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since 1991, SPM risk has decreased significantly among patients with oropharyngeal SCC (annual percentage change in EAR, -4.6%; P = .03). CONCLUSION: In patients with HNSCC, the risk and distribution of SPM differ significantly according to subsite of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried the highest excess risk of SPM. Since then, during the HPV era, SPM risk associated with oropharyngeal SCC has declined to the lowest risk level of any subsite
— id: 134130, year: 2011, vol: 29, page: 739, stat: Journal Article,

Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels
Parikh, Hemang; Wang, Zhaoming; Pettigrew, Kerry A; Jia, Jinping; Daugherty, Sarah; Yeager, Meredith; Jacobs, Kevin B; Hutchinson, Amy; Burdett, Laura; Cullen, Michael; Qi, Liqun; Boland, Joseph; Collins, Irene; Albert, Thomas J; Vatten, Lars J; Hveem, Kristian; Njolstad, Inger; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Virtamo, Jarmo; Thun, Michael J; Feigelson, Heather Spencer; Diver, W Ryan; Chatterjee, Nilanjan; Thomas, Gilles; Albanes, Demetrius; Chanock, Stephen J; Hunter, David J; Hoover, Robert; Hayes, Richard B; Berndt, Sonja I; Sampson, Joshua; Amundadottir, Laufey
2011 Jun;129(6):675-685, Human genetics
Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56 kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case-control studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P = 0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P = 3.41 x 10(-4), per-allele trend odds ratio (OR) = 0.77, 95% CI = 0.67-0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score <7 and disease stage <III (P = 4.72 x 10(-5), per-allele trend OR = 0.68, 95% CI = 0.57-0.82) and not for advanced cases with Gleason score >8 or stage >/=III (P = 0.31, per-allele trend OR = 1.12, 95% CI = 0.90-1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61 ng/ml, 95% CI = 1.49-1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12 ng/ml, 95% CI = 0.96-1.28) (P = 9.70 x 10(-5)). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy
— id: 134282, year: 2011, vol: 129, page: 675, stat: Journal Article,

Meta-analysis of new genome-wide association studies of colorectal cancer risk
Peters U; Hutter CM; Hsu L; Schumacher FR; Conti DV; Carlson CS; Edlund CK; Haile RW; Gallinger S; Zanke BW; Lemire M; Rangrej J; Vijayaraghavan R; Chan AT; Hazra A; Hunter DJ; Ma J; Fuchs CS; Giovannucci EL; Kraft P; Liu Y; Chen L; Jiao S; Makar KW; Taverna D; Gruber SB; Rennert G; Moreno V; Ulrich CM; Woods MO; Green RC; Parfrey PS; Prentice RL; Kooperberg C; Jackson RD; Lacroix AZ; Caan BJ; Hayes RB; Berndt SI; Chanock SJ; Schoen RE; Chang-Claude J; Hoffmeister M; Brenner H; Frank B; Bezieau S; Kury S; Slattery ML; Hopper JL; Jenkins MA; Le Marchand L; Lindor NM; Newcomb PA; Seminara D; Hudson TJ; Duggan DJ; Potter JD; Casey G
2011 Feb;131(2):217-234, Human genetics
Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 x 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 x 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 x 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer
— id: 139039, year: 2011, vol: 131, page: 217, stat: Journal Article,

Genome-wide association study of relative telomere length
Prescott, Jennifer; Kraft, Peter; Chasman, Daniel I; Savage, Sharon A; Mirabello, Lisa; Berndt, Sonja I; Weissfeld, Joel L; Han, Jiali; Hayes, Richard B; Chanock, Stephen J; Hunter, David J; De Vivo, Immaculata
2011 ;6(5):e19635-e19635, PLoS ONE
Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele beta = -0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect beta estimates as small as +/-0.10 for SNPs with minor allele frequencies of >/=0.15 at genome-wide significance. However, power is greatly reduced for beta estimates smaller than +/-0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed
— id: 134515, year: 2011, vol: 6, page: e19635, stat: Journal Article,

Association Between Oral Health And Gastric Precancerous Lesions
Salazar CR; Francois F; Li Y; Corby P; Hays R; Leung C; Bedi S; Segers S; Queiroz E; Sun J; Wang B; Ho H; Craig R; Cruz G; Blaser MJ; Perez-Perez G; Hayes RB; Dasanayake A; Pei Z; Chen Y
2011 Dec 1;:399-403 #, Carcinogenesis
Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared to non-cases, cases were significantly more likely to not floss their teeth (Odds Ratio [OR] = 2.89, 95% Confidence Interval [CI]: 1.09-7.64), adjusting for age, sex, race, BMI, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n=28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases (OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites [equivalent to 19.7%]), independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions
— id: 147670, year: 2011, vol: , page: 399, stat: Journal Article,

Genome-wide association study identifies new prostate cancer susceptibility loci
Schumacher, Fredrick R; Berndt, Sonja I; Siddiq, Afshan; Jacobs, Kevin B; Wang, Zhaoming; Lindstrom, Sara; Stevens, Victoria L; Chen, Constance; Mondul, Alison M; Travis, Ruth C; Stram, Daniel O; Eeles, Rosalind A; Easton, Douglas F; Giles, Graham; Hopper, John L; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Kenneth; Al Olama, Ali Amin; Kote-Jarai, Zsofia; Guy, Michelle; Severi, Gianluca; Gronberg, Henrik; Isaacs, William B; Karlsson, Robert; Wiklund, Fredrik; Xu, Jianfeng; Allen, Naomi E; Andriole, Gerald L; Barricarte, Aurelio; Boeing, Heiner; Bas Bueno-de-Mesquita, H; Crawford, E David; Diver, W Ryan; Gonzalez, Carlos A; Gaziano, J Michael; Giovannucci, Edward L; Johansson, Mattias; Le Marchand, Loic; Ma, Jing; Sieri, Sabina; Stattin, Par; Stampfer, Meir J; Tjonneland, Anne; Vineis, Paolo; Virtamo, Jarmo; Vogel, Ulla; Weinstein, Stephanie J; Yeager, Meredith; Thun, Michael J; Kolonel, Laurence N; Henderson, Brian E; Albanes, Demetrius; Hayes, Richard B; Spencer Feigelson, Heather; Riboli, Elio; Hunter, David J; Chanock, Stephen J; Haiman, Christopher A; Kraft, Peter
2011 Oct 1;20(19):3867-3875, Human molecular genetics
Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade >/= 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 x 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 x 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes
— id: 137918, year: 2011, vol: 20, page: 3867, stat: Journal Article,

Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial
Sigurdson, Alice J; Jones, Irene M; Wei, Qingyi; Wu, Xifeng; Spitz, Margaret R; Stram, Douglas A; Gross, Myron D; Huang, Wen-Yi; Wang, Li-E; Gu, Jian; Thomas, Cynthia B; Reding, Douglas J; Hayes, Richard B; Caporaso, Neil E
2011 Jan;32(1):69-73, Carcinogenesis
Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk
— id: 134219, year: 2011, vol: 32, page: 69, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Abnet, Christian C; Chen, Yu; Chow, Wong-Ho; Gao, Yu-Tang; Helzlsouer, Kathy J; Le Marchand, Loic; McCullough, Marjorie L; Shikany, James M; Virtamo, Jarmo; Weinstein, Stephanie J; Xiang, Yong-Bing; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Arslan, Alan A; Campbell, David S; Campbell, Peter T; Hayes, Richard B; Horst, Ronald L; Kolonel, Laurence N; Nomura, Abraham M Y; Purdue, Mark P; Snyder, Kirk; Shu, Xiao-Ou
2010 Jul 1;172(1):94-106, American journal of epidemiology
Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers
— id: 114065, year: 2010, vol: 172, page: 94, stat: Journal Article,

Genome-wide association study of circulating vitamin D levels
Ahn, Jiyoung; Yu, Kai; Stolzenberg-Solomon, Rachael; Simon, K Claire; McCullough, Marjorie L; Gallicchio, Lisa; Jacobs, Eric J; Ascherio, Alberto; Helzlsouer, Kathy; Jacobs, Kevin B; Li, Qizhai; Weinstein, Stephanie J; Purdue, Mark; Virtamo, Jarmo; Horst, Ronald; Wheeler, William; Chanock, Stephen; Hunter, David J; Hayes, Richard B; Kraft, Peter; Albanes, Demetrius
2010 Jul 1;19(13):2739-2745, Human molecular genetics
The primary circulating form of vitamin D, 25-hydroxy-vitamin D [25(OH)D], is associated with multiple medical outcomes, including rickets, osteoporosis, multiple sclerosis and cancer. In a genome-wide association study (GWAS) of 4501 persons of European ancestry drawn from five cohorts, we identified single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (vitamin D binding) protein, GC, on chromosome 4q12-13 that were associated with 25(OH)D concentrations: rs2282679 (P=2.0x10(-30)), in linkage disequilibrium (LD) with rs7041, a non-synonymous SNP (D432E; P=4.1x10(-22)) and rs1155563 (P=3.8x10(-25)). Suggestive signals for association with 25(OH)D were also observed for SNPs in or near three other genes involved in vitamin D synthesis or activation: rs3829251 on chromosome 11q13.4 in NADSYN1 [encoding nicotinamide adenine dinucleotide (NAD) synthetase; P=8.8x10(-7)], which was in high LD with rs1790349, located in DHCR7, the gene encoding 7-dehydrocholesterol reductase that synthesizes cholesterol from 7-dehydrocholesterol; rs6599638 in the region harboring the open-reading frame 88 (C10orf88) on chromosome 10q26.13 in the vicinity of ACADSB (acyl-Coenzyme A dehydrogenase), involved in cholesterol and vitamin D synthesis (P=3.3x10(-7)); and rs2060793 on chromosome 11p15.2 in CYP2R1 (cytochrome P450, family 2, subfamily R, polypeptide 1, encoding a key C-25 hydroxylase that converts vitamin D3 to an active vitamin D receptor ligand; P=1.4x10(-5)). We genotyped SNPs in these four regions in 2221 additional samples and confirmed strong genome-wide significant associations with 25(OH)D through meta-analysis with the GWAS data for GC (P=1.8x10(-49)), NADSYN1/DHCR7 (P=3.4x10(-9)) and CYP2R1 (P=2.9x10(-17)), but not C10orf88 (P=2.4x10(-5))
— id: 110094, year: 2010, vol: 19, page: 2739, stat: Journal Article,

Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin
Chu, Lisa W; Meyer, Tamra E; Li, Qizhai; Menashe, Idan; Yu, Kai; Rosenberg, Philip S; Huang, Wen-Yi; Quraishi, Sabah M; Kaaks, Rudolf; Weiss, Jocelyn M; Hayes, Richard B; Chanock, Stephen J; Hsing, Ann W
2010 Jul;19(7):1848-1854, Cancer epidemiology biomarkers & prevention
BACKGROUND: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. METHODS: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels. RESULTS: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05). CONCLUSIONS: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels. Impact: These results might provide some clues for the strong link between 8q24 and prostate cancer risk
— id: 139028, year: 2010, vol: 19, page: 1848, stat: Journal Article,

PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3)
Dossus, Laure; Kaaks, Rudolf; Canzian, Federico; Albanes, Demetrius; Berndt, Sonja I; Boeing, Heiner; Buring, Julie; Chanock, Stephen J; Clavel-Chapelon, Francoise; Feigelson, Heather Spencer; Gaziano, John M; Giovannucci, Edward; Gonzalez, Carlos; Haiman, Christopher A; Hallmans, Goran; Hankinson, Susan E; Hayes, Richard B; Henderson, Brian E; Hoover, Robert N; Hunter, David J; Khaw, Kay-Tee; Kolonel, Laurence N; Kraft, Peter; Ma, Jing; Le Marchand, Loic; Lund, Eiliv; Peeters, Petra H M; Stampfer, Meir; Stram, Dan O; Thomas, Gilles; Thun, Michael J; Tjonneland, Anne; Trichopoulos, Dimitrios; Tumino, Rosario; Riboli, Elio; Virtamo, Jarmo; Weinstein, Stephanie J; Yeager, Meredith; Ziegler, Regina G; Cox, David G
2010 Mar;31(3):455-461, Carcinogenesis
Genes involved in the inflammation pathway have been associated with cancer risk. Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers. We conducted a study within the Breast and Prostate Cancer Cohort Consortium to examine the association between IL6 and PTGS2 polymorphisms and breast and prostate cancer risk. Twenty-seven polymorphisms, selected by pairwise tagging, were genotyped on 6292 breast cancer cases and 8135 matched controls and 8008 prostate cancer cases and 8604 matched controls. The large sample sizes and comprehensive single nucleotide polymorphism tagging in this study gave us excellent power to detect modest effects for common variants. After adjustment for multiple testing, none of the associations examined remained statistically significant at P = 0.01. In analyses not adjusted for multiple testing, one IL6 polymorphism (rs6949149) was marginally associated with breast cancer risk (TT versus GG, odds ratios (OR): 1.32; 99% confidence intervals (CI): 1.00-1.74, P(trend) = 0.003) and two were marginally associated with prostate cancer risk (rs6969502-AA versus rs6969502-GG, OR: 0.87, 99% CI: 0.75-1.02; P(trend) = 0.002 and rs7805828-AA versus rs7805828-GG, OR: 1.11, 99% CI: 0.99-1.26; P(trend) = 0.007). An increase in breast cancer risk was observed for the PTGS2 polymorphism rs7550380 (TT versus GG, OR: 1.38, 99% CI: 1.04-1.83). No association was observed between PTGS2 polymorphisms and prostate cancer risk. In conclusion, common genetic variation in these two genes might play at best a limited role in breast and prostate cancers
— id: 139020, year: 2010, vol: 31, page: 455, stat: Journal Article,

Xenobiotic metabolizing genes, meat-related exposures, and risk of advanced colorectal adenoma
Ferrucci, Lea M; Cross, Amanda J; Gunter, Marc J; Ahn, Jiyoung; Mayne, Susan T; Ma, Xiaomei; Chanock, Stephen J; Yeager, Meredith; Graubard, Barry I; Berndt, Sonja I; Huang, Wen-Yi; Hayes, Richard B; Sinha, Rashmi
2010 ;3(4-6):170-181, Journal of nutrigenetics & nutrigenomics
— id: 139034, year: 2010, vol: 3, page: 170, stat: Journal Article,

Xenobiotic metabolizing genes, meat-related exposures, and risk of advanced colorectal adenoma
Ferrucci, Leah M; Cross, Amanda J; Gunter, Marc J; Ahn, Jiyoung; Mayne, Susan T; Ma, Xiaomei; Chanock, Stephen J; Yeager, Meredith; Graubard, Barry I; Berndt, Sonja I; Huang, Wen-Yi; Hayes, Richard B; Sinha, Rashmi
2010 ;101:34-45, World review of nutrition & dietetics
— id: 139025, year: 2010, vol: 101, page: 34, stat: Journal Article,

Coffee and tea intake and risk of head and neck cancer: pooled analysis in the international head and neck cancer epidemiology consortium
Galeone, Carlotta; Tavani, Alessandra; Pelucchi, Claudio; Turati, Federica; Winn, Deborah M; Levi, Fabio; Yu, Guo-Pei; Morgenstern, Hal; Kelsey, Karl; Dal Maso, Luigino; Purdue, Mark P; McClean, Michael; Talamini, Renato; Hayes, Richard B; Franceschi, Silvia; Schantz, Stimson; Zhang, Zuo-Feng; Ferro, Gilles; Chuang, Shu-Chun; Boffetta, Paolo; La Vecchia, Carlo; Hashibe, Mia
2010 Jul;19(7):1723-1736, Cancer epidemiology biomarkers & prevention
BACKGROUND: Only a few studies have explored the relation between coffee and tea intake and head and neck cancers, with inconsistent results. METHODS: We pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for potential confounders. RESULTS: Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94-0.98) for an increment of 1 cup per day and 0.61 (95% CI, 0.47-0.80) in drinkers of >4 cups per day versus nondrinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46; 95% CI, 0.30-0.71 for oral cavity; OR, 0.58; 95% CI, 0.41-0.82 for oropharynx/hypopharynx; and OR, 0.61; 95% CI, 0.37-1.01 for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; 95% CI, 0.64-1.45 in drinkers of >4 cups per day versus nondrinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk (OR, 0.99; 95% CI, 0.89-1.11 for drinkers versus nondrinkers). CONCLUSIONS: This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx. IMPACT: Given widespread use of coffee and the relatively high incidence and low survival of head and neck cancers, the observed inverse association may have appreciable public health relevance
— id: 139029, year: 2010, vol: 19, page: 1723, stat: Journal Article,

Circulating 25-hydroxyvitamin D and the risk of rarer cancers: Design and methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Gallicchio, Lisa; Helzlsouer, Kathy J; Chow, Wong-Ho; Freedman, D Michal; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Koenig, Karen L; Kolonel, Laurence N; Laden, Francine; McCullough, Marjorie L; Parisi, Dominick; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Stolzenberg-Solomon, Rachael Z; Tworoger, Shelley S; Varanasi, Arti; Virtamo, Jarmo; Wilkens, Lynne R; Xiang, Yong-Bing; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Abnet, Christian C; Albanes, Demetrius; Bertrand, Kimberly; Weinstein, Stephanie J
2010 Jul 1;172(1):10-20, American journal of epidemiology
The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974-2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50-<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations
— id: 134375, year: 2010, vol: 172, page: 10, stat: Journal Article,

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium
Gaudet, Mia M; Olshan, Andrew F; Chuang, Shu-Chun; Berthiller, Julien; Zhang, Zuo-Feng; Lissowska, Jolanta; Zaridze, David; Winn, Deborah M; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neolilia; Sturgis, Erich M; Schwartz, Stephen M; Rudnai, Peter; Eluf-Neto, Jose; Muscat, Joshua; Morgenstern, Hal; Menezes, Ana; Matos, Elena; Bucur, Alexandru; Levi, Fabio; Lazarus, Philip; La Vecchia, Carlo; Koifman, Sergio; Kelsey, Karl; Herrero, Rolando; Hayes, Richard B; Franceschi, Silva; Wunsch-Filho, Victor; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Dal Maso, Luigino; Curado, Maria Paula; Chen, Chu; Castellsague, Xavier; Benhamou, Simone; Boffetta, Paolo; Brennan, Paul; Hashibe, Mia
2010 Aug;39(4):1091-1102, International journal of epidemiology
BACKGROUND: Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. METHODS: We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. RESULTS: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < or =18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI > or =30 kg/m(2) (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < or =18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. CONCLUSIONS: In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies
— id: 139022, year: 2010, vol: 39, page: 1091, stat: Journal Article,

Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer
Gu, Fangyi; Schumacher, Fredrick R; Canzian, Federico; Allen, Naomi E; Albanes, Demetrius; Berg, Christine D; Berndt, Sonja I; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Buring, Julie E; Chabbert-Buffet, Nathalie; Chanock, Stephen J; Clavel-Chapelon, Francoise; Dumeaux, Vanessa; Gaziano, J Michael; Giovannucci, Edward L; Haiman, Christopher A; Hankinson, Susan E; Hayes, Richard B; Henderson, Brian E; Hunter, David J; Hoover, Robert N; Johansson, Mattias; Key, Timothy J; Khaw, Kay-Tee; Kolonel, Laurence N; Lagiou, Pagona; Lee, I-Min; LeMarchand, Loic; Lund, Eiliv; Ma, Jing; Onland-Moret, N Charlotte; Overvad, Kim; Rodriguez, Laudina; Sacerdote, Carlotta; Sanchez, Maria-Jose; Stampfer, Meir J; Stattin, Par; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Tjonneland, Anne; Trichopoulos, Dimitrios; Tumino, Rosario; Virtamo, Jarmo; Weinstein, Stephanie J; Willett, Walter C; Yeager, Meredith; Zhang, Shumin M; Kaaks, Rudolf; Riboli, Elio; Ziegler, Regina G; Kraft, Peter
2010 Nov;19(11):2877-2887, Cancer epidemiology biomarkers & prevention
BACKGROUND: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins. METHODS: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium. RESULTS: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 x 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R(2) = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers. CONCLUSION: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women. IMPACT: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes
— id: 139031, year: 2010, vol: 19, page: 2877, stat: Journal Article,

Re: Mortality From Lymphohematopoietic Malignancies and Brain Cancer Among Embalmers Exposed to Formaldehyde Response
Hauptmann, M.; Stewart, P. A.; Lubin, J. H.; Freeman, L. E. Beane; Hornung, R. W.; Herrick, R. F.; Hoover, R. N.; Fraumeni, J. F., Jr.; Blair, A.; Hayes, R. B.
2010 OCT ;102(19):1519-1520, Journal of the National Cancer Institute
— id: 114011, year: 2010, vol: 102, page: 1519, stat: Journal Article,

Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium
Heck, Julia E; Berthiller, Julien; Vaccarella, Salvatore; Winn, Deborah M; Smith, Elaine M; Shan'gina, Oxana; Schwartz, Stephen M; Purdue, Mark P; Pilarska, Agnieszka; Eluf-Neto, Jose; Menezes, Ana; McClean, Michael D; Matos, Elena; Koifman, Sergio; Kelsey, Karl T; Herrero, Rolando; Hayes, Richard B; Franceschi, Silvia; Wunsch-Filho, Victor; Fernandez, Leticia; Daudt, Alexander W; Curado, Maria Paula; Chen, Chu; Castellsague, Xavier; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia
2010 Feb;39(1):166-181, International journal of epidemiology
BACKGROUND: Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). METHODS: We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite. RESULTS: Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). CONCLUSIONS: Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection
— id: 134987, year: 2010, vol: 39, page: 166, stat: Journal Article,

Long-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Hofmann, Jonathan N; Yu, Kai; Horst, Ronald L; Hayes, Richard B; Purdue, Mark P
2010 Apr;19(4):927-931, Cancer epidemiology biomarkers & prevention
Molecular epidemiologic studies of vitamin D and risk of cancer and other health outcomes usually involve a single measurement of the biomarker 25-hydroxyvitamin D [25(OH)D] in serum or plasma. However, the extent to which 25(OH)D concentration at a single time point is representative of an individual's long-term vitamin D status is unclear. To address this question, we evaluated within-person variability in 25(OH)D concentrations across serum samples collected at three time points over a 5-year period among 29 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Blood collection took place year-round, although samples for a given participant were collected in the same month each year. The within-person coefficient of variation and intraclass correlation coefficient were calculated using variance components estimated from random effects models. Spearman rank correlation coefficients were calculated to evaluate agreement between measurements at different collection times (baseline, +1 year, +5 years). The within-subject coefficient of variation was 14.9% [95% confidence interval (CI), 12.4-18.1%] and the intraclass correlation coefficient was 0.71 (95% CI, 0.63-0.88). Spearman rank correlation coefficients comparing baseline to +1 year, +1 year to +5 years, and baseline to +5 years were 0.65 (95% CI, 0.37-0.82), 0.61 (0.29-0.81), and 0.53 (0.17-0.77), respectively. Slightly stronger correlations were observed after restricting to non-Hispanic Caucasian subjects. These findings suggest that serum 25(OH)D concentration at a single time point may be a useful biomarker of long-term vitamin D status in population-based studies of various diseases
— id: 133496, year: 2010, vol: 19, page: 927, stat: Journal Article,

Non-steroidal anti-inflammatory drug use and colorectal polyps in the Prostate, Lung, Colorectal, And Ovarian Cancer Screening Trial
Johnson, Christine Cole; Hayes, Richard B; Schoen, Robert E; Gunter, Marc J; Huang, Wen-Yi
2010 Dec;105(12):2646-2655, American journal of gastroenterology
OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in animal and human studies to reduce risk for colorectal cancer and adenomatous polyps, but risk modification for subgroups of the population and effects on hyperplastic polyps have been less studied. METHODS: Data on recent use of two frequently ingested NSAIDs, aspirin and ibuprofen, were collected at baseline from participants aged 55-74 years in the 10 centers of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants randomized to the intervention arm of the trial received a flexible sigmoidoscopy during a baseline examination. Follow-up of detected polyps was accomplished outside the Trial setting and relevant records were sought and abstracted. Cases (n=4,017) included subjects with a biopsy-proven polyp in the left side of the colon (descending colon, sigmoid, and rectum) detected as a consequence of PLCO screening; controls (n=38,396) were subjects with no left-sided colon polyp. RESULTS: Regular use of aspirin (>/= 4 times/month) in the past year was inversely associated with hyperplastic polyps (odds ratios (OR)=0.8, 95% confidence interval (CI)=0.7-0.9), adenomatous polyps (OR=0.8, 95% CI=0.8-0.9), and advanced adenomas (OR=0.8, 95% CI=0.7-0.9). As frequency of aspirin use increased, the prevalence of polyps decreased significantly for each histological classification (P for trend </= 0.0004). Similar patterns were found for adenomas and ibuprofen. Overall protection was consistent in both the descending colon or sigmoid and the rectum, but more evident in males. In males, the OR for heavy use of combined aspirin and ibuprofen (>/= 2 times/day) was 0.6 (95% CI=0.5-0.8), as opposed to 0.9 (95% CI=0.8-1.1) in females. The protective effects of NSAIDs for females were apparent only among those with body mass index (BMI) <25 (OR=0.8, 95% CI=0.7-1.0 for regular use of NSAIDs; P interaction=0.04). We also found a slightly stronger protection of NSAIDs in the 70-74 years age group compared with those aged 55-69 years. CONCLUSIONS: This study of a large general risk population supports previous work that recent use of aspirin and ibuprofen is associated with a decreased risk of colorectal adenomas and demonstrates that this protective effect may be stronger in certain population subgroups and is also evident for aspirin and hyperplastic polyps
— id: 139030, year: 2010, vol: 105, page: 2646, stat: Journal Article,

Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis
Kocarnik, Jonathan D; Hutter, Carolyn M; Slattery, Martha L; Berndt, Sonja I; Hsu, Li; Duggan, David J; Muehling, Jill; Caan, Bette J; Beresford, Shirley A A; Rajkovic, Aleksandar; Sarto, Gloria E; Marshall, James R; Hammad, Nazik; Wallace, Robert B; Makar, Karen W; Prentice, Ross L; Potter, John D; Hayes, Richard B; Peters, Ulrike
2010 Dec;19(12):3131-3139, Cancer epidemiology biomarkers & prevention
BACKGROUND: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive. METHODS: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women's Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions. RESULTS: SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI, 1.01-1.40; P(trend) = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI, 0.99-1.25; P(trend) = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03-1.12; P(trend) = 0.001). CONCLUSIONS: Our results suggest the Aallele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies. IMPACT: If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia
— id: 133842, year: 2010, vol: 19, page: 3131, stat: Journal Article,

Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer
Koutros, Stella; Schumacher, Fredrick R; Hayes, Richard B; Ma, Jing; Huang, Wen-Yi; Albanes, Demetrius; Canzian, Federico; Chanock, Stephen J; Crawford, E David; Diver, W Ryan; Feigelson, Heather Spencer; Giovanucci, Edward; Haiman, Christopher A; Henderson, Brian E; Hunter, David J; Kaaks, Rudolf; Kolonel, Laurence N; Kraft, Peter; Le Marchand, Loic; Riboli, Elio; Siddiq, Afshan; Stampfer, Mier J; Stram, Daniel O; Thomas, Gilles; Travis, Ruth C; Thun, Michael J; Yeager, Meredith; Berndt, Sonja I
2010 Mar 15;70(6):2389-2396, Cancer research
The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. Thus, we explored the association between single-nucleotide polymorphisms (SNP) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk [OR(per allele), 1.08 (95% CI, 1.03-1.14); P(trend) = 0.0017] after adjustment for multiple testing (P(adj) = 0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association [OR(per allele), 1.21 (95% CI, 1.09-1.34); P(trend) = 0.0003]. The adjusted association was stronger for men who were diagnosed before the age of 65 years [OR(per allele), 1.47 (95% CI, 1.20-1.79); P(trend) = 0.0001] or had a family history [OR(per allele) = 1.57 (95% CI, 1.11-2.23); P(trend) = 0.0114], and was strongest in those with both characteristics [OR(per allele) = 2.31 (95% CI, 1.07-5.07), P-interaction = 0.005]. Increased risks were observed among men in the top tertile of circulating insulin-like growth factor-I (IGF-I) levels [OR(per allele) = 1.46 (95% CI, 1.04-2.06); P(trend) = 0.075]. No differences were observed with disease aggressiveness (Gleason grade >or=8 or stage T(3)/T(4) or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early-onset disease, which may be attributable to IGF-dependent PI3K signaling
— id: 133490, year: 2010, vol: 70, page: 2389, stat: Journal Article,

Hundreds of variants clustered in genomic loci and biological pathways affect human height
Lango Allen, Hana; Estrada, Karol; Lettre, Guillaume; Berndt, Sonja I; Weedon, Michael N; Rivadeneira, Fernando; Willer, Cristen J; Jackson, Anne U; Vedantam, Sailaja; Raychaudhuri, Soumya; Ferreira, Teresa; Wood, Andrew R; Weyant, Robert J; Segre, Ayellet V; Speliotes, Elizabeth K; Wheeler, Eleanor; Soranzo, Nicole; Park, Ju-Hyun; Yang, Jian; Gudbjartsson, Daniel; Heard-Costa, Nancy L; Randall, Joshua C; Qi, Lu; Vernon Smith, Albert; Magi, Reedik; Pastinen, Tomi; Liang, Liming; Heid, Iris M; Luan, Jian'an; Thorleifsson, Gudmar; Winkler, Thomas W; Goddard, Michael E; Sin Lo, Ken; Palmer, Cameron; Workalemahu, Tsegaselassie; Aulchenko, Yurii S; Johansson, Asa; Zillikens, M Carola; Feitosa, Mary F; Esko, Tonu; Johnson, Toby; Ketkar, Shamika; Kraft, Peter; Mangino, Massimo; Prokopenko, Inga; Absher, Devin; Albrecht, Eva; Ernst, Florian; Glazer, Nicole L; Hayward, Caroline; Hottenga, Jouke-Jan; Jacobs, Kevin B; Knowles, Joshua W; Kutalik, Zoltan; Monda, Keri L; Polasek, Ozren; Preuss, Michael; Rayner, Nigel W; Robertson, Neil R; Steinthorsdottir, Valgerdur; Tyrer, Jonathan P; Voight, Benjamin F; Wiklund, Fredrik; Xu, Jianfeng; Zhao, Jing Hua; Nyholt, Dale R; Pellikka, Niina; Perola, Markus; Perry, John R B; Surakka, Ida; Tammesoo, Mari-Liis; Altmaier, Elizabeth L; Amin, Najaf; Aspelund, Thor; Bhangale, Tushar; Boucher, Gabrielle; Chasman, Daniel I; Chen, Constance; Coin, Lachlan; Cooper, Matthew N; Dixon, Anna L; Gibson, Quince; Grundberg, Elin; Hao, Ke; Juhani Junttila, M; Kaplan, Lee M; Kettunen, Johannes; Konig, Inke R; Kwan, Tony; Lawrence, Robert W; Levinson, Douglas F; Lorentzon, Mattias; McKnight, Barbara; Morris, Andrew P; Muller, Martina; Suh Ngwa, Julius; Purcell, Shaun; Rafelt, Suzanne; Salem, Rany M; Salvi, Erika; Sanna, Serena; Shi, Jianxin; Sovio, Ulla; Thompson, John R; Turchin, Michael C; Vandenput, Liesbeth; Verlaan, Dominique J; Vitart, Veronique; White, Charles C; Ziegler, Andreas; Almgren, Peter; Balmforth, Anthony J; Campbell, Harry; Citterio, Lorena; De Grandi, Alessandro; Dominiczak, Anna; Duan, Jubao; Elliott, Paul; Elosua, Roberto; Eriksson, Johan G; Freimer, Nelson B; Geus, Eco J C; Glorioso, Nicola; Haiqing, Shen; Hartikainen, Anna-Liisa; Havulinna, Aki S; Hicks, Andrew A; Hui, Jennie; Igl, Wilmar; Illig, Thomas; Jula, Antti; Kajantie, Eero; Kilpelainen, Tuomas O; Koiranen, Markku; Kolcic, Ivana; Koskinen, Seppo; Kovacs, Peter; Laitinen, Jaana; Liu, Jianjun; Lokki, Marja-Liisa; Marusic, Ana; Maschio, Andrea; Meitinger, Thomas; Mulas, Antonella; Pare, Guillaume; Parker, Alex N; Peden, John F; Petersmann, Astrid; Pichler, Irene; Pietilainen, Kirsi H; Pouta, Anneli; Ridderstrale, Martin; Rotter, Jerome I; Sambrook, Jennifer G; Sanders, Alan R; Schmidt, Carsten Oliver; Sinisalo, Juha; Smit, Jan H; Stringham, Heather M; Bragi Walters, G; Widen, Elisabeth; Wild, Sarah H; Willemsen, Gonneke; Zagato, Laura; Zgaga, Lina; Zitting, Paavo; Alavere, Helene; Farrall, Martin; McArdle, Wendy L; Nelis, Mari; Peters, Marjolein J; Ripatti, Samuli; van Meurs, Joyce B J; Aben, Katja K; Ardlie, Kristin G; Beckmann, Jacques S; Beilby, John P; Bergman, Richard N; Bergmann, Sven; Collins, Francis S; Cusi, Daniele; den Heijer, Martin; Eiriksdottir, Gudny; Gejman, Pablo V; Hall, Alistair S; Hamsten, Anders; Huikuri, Heikki V; Iribarren, Carlos; Kahonen, Mika; Kaprio, Jaakko; Kathiresan, Sekar; Kiemeney, Lambertus; Kocher, Thomas; Launer, Lenore J; Lehtimaki, Terho; Melander, Olle; Mosley, Tom H Jr; Musk, Arthur W; Nieminen, Markku S; O'Donnell, Christopher J; Ohlsson, Claes; Oostra, Ben; Palmer, Lyle J; Raitakari, Olli; Ridker, Paul M; Rioux, John D; Rissanen, Aila; Rivolta, Carlo; Schunkert, Heribert; Shuldiner, Alan R; Siscovick, David S; Stumvoll, Michael; Tonjes, Anke; Tuomilehto, Jaakko; van Ommen, Gert-Jan; Viikari, Jorma; Heath, Andrew C; Martin, Nicholas G; Montgomery, Grant W; Province, Michael A; Kayser, Manfred; Arnold, Alice M; Atwood, Larry D; Boerwinkle, Eric; Chanock, Stephen J; Deloukas, Panos; Gieger, Christian; Gronberg, Henrik; Hall, Per; Hattersley, Andrew T; Hengstenberg, Christian; Hoffman, Wolfgang; Lathrop, G Mark; Salomaa, Veikko; Schreiber, Stefan; Uda, Manuela; Waterworth, Dawn; Wright, Alan F; Assimes, Themistocles L; Barroso, Ines; Hofman, Albert; Mohlke, Karen L; Boomsma, Dorret I; Caulfield, Mark J; Cupples, L Adrienne; Erdmann, Jeanette; Fox, Caroline S; Gudnason, Vilmundur; Gyllensten, Ulf; Harris, Tamara B; Hayes, Richard B; Jarvelin, Marjo-Riitta; Mooser, Vincent; Munroe, Patricia B; Ouwehand, Willem H; Penninx, Brenda W; Pramstaller, Peter P; Quertermous, Thomas; Rudan, Igor; Samani, Nilesh J; Spector, Timothy D; Volzke, Henry; Watkins, Hugh; Wilson, James F; Groop, Leif C; Haritunians, Talin; Hu, Frank B; Kaplan, Robert C; Metspalu, Andres; North, Kari E; Schlessinger, David; Wareham, Nicholas J; Hunter, David J; O'Connell, Jeffrey R; Strachan, David P; Wichmann, H-Erich; Borecki, Ingrid B; van Duijn, Cornelia M; Schadt, Eric E; Thorsteinsdottir, Unnur; Peltonen, Leena; Uitterlinden, Andre G; Visscher, Peter M; Chatterjee, Nilanjan; Loos, Ruth J F; Boehnke, Michael; McCarthy, Mark I; Ingelsson, Erik; Lindgren, Cecilia M; Abecasis, Goncalo R; Stefansson, Kari; Frayling, Timothy M; Hirschhorn, Joel N
2010 Oct 14;467(7317):832-838, Nature
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
— id: 138021, year: 2010, vol: 467, page: 832, stat: Journal Article,

Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies
Lindstrom, Sara; Hunter, David J; Gronberg, Henrik; Stattin, Par; Wiklund, Fredrik; Xu, Jianfeng; Chanock, Stephen J; Hayes, Richard; Kraft, Peter
2010 Mar;19(3):873-876, Cancer epidemiology biomarkers & prevention
BACKGROUND: Genetic variation in two members of the Toll-like receptor family, TLR4 and the gene cluster TLR6-1-10, has been implicated in prostate cancer in several studies but the associated alleles have not been consistent across reports. METHODS: We did a pooled analysis combining genotype data from three case-control studies, Cancer of the Prostate in Sweden, the Health Professionals Follow-up Study, and the Prostate, Lung, Colon and Ovarian Cancer Screening Trial, with data from 3,101 prostate cancer cases and 2,523 controls. We did imputation to obtain dense coverage of the genes and comparable genotype data for all cohorts. In total, 58 single nucleotide polymorphisms in TLR4 and 96 single nucleotide polymorphisms in TLR6-1-10 were genotyped or imputed and analyzed in the entire data set. We did a cohort-specific analysis as well as meta-analysis and pooled analysis. We also evaluated whether the analyses differed by age or disease severity. RESULTS: We observed no overall association between genetic variation at the TLR4 and TLR6-1-10 loci and risk of prostate cancer. CONCLUSIONS: Common germ line genetic variation in TLR4 and TLR6-1-10 did not seem to have a strong association with risk of prostate cancer. IMPACT: This study suggests that earlier associations between prostate cancer risk and TLR4 and TLR6-1-10 sequence variants were chance findings. To definitely assess the causal relationship between TLR sequence variants and prostate cancer risk, very large sample sizes are needed
— id: 139023, year: 2010, vol: 19, page: 873, stat: Journal Article,

A large study of androgen receptor germline variants and their relation to sex hormone levels and prostate cancer risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Lindstrom, Sara; Ma, Jing; Altshuler, David; Giovannucci, Edward; Riboli, Elio; Albanes, Demetrius; Allen, Naomi E; Berndt, Sonja I; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Chanock, Stephen J; Dunning, Alison M; Feigelson, Heather Spencer; Gaziano, J Michael; Haiman, Christopher A; Hayes, Richard B; Henderson, Brian E; Hunter, David J; Kaaks, Rudolf; Kolonel, Laurence N; Le Marchand, Loic; Martinez, Carmen; Overvad, Kim; Siddiq, Afshan; Stampfer, Meir; Stattin, Par; Stram, Daniel O; Thun, Michael J; Trichopoulos, Dimitrios; Tumino, Rosario; Virtamo, Jarmo; Weinstein, Stephanie J; Yeager, Meredith; Kraft, Peter; Freedman, Matthew L
2010 Sep;95(9):E121-E127, Journal of clinical endocrinology & metabolism
BACKGROUND: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. OBJECTIVE AND METHODS: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. RESULTS: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 x 10(-5)) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). CONCLUSIONS: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol
— id: 134359, year: 2010, vol: 95, page: E121, stat: Journal Article,

Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinoma
Lubahn, Jessica; Berndt, Sonja I; Jin, Carol H; Klim, Aleksandra; Luly, Jason; Wu, William S; Isaacs, Sarah; Wiley, Kathleen; Isaacs, William B; Suarez, Brian K; Hayes, Richard B; Kibel, Adam S
2010 May 1;70(6):646-653, Prostate
BACKGROUND: Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. METHODS: We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS: The H allele was associated with a reduced risk of aggressive PCa (OR(per allele) = 0.67, 95% CI: 0.54-0.83, P(trend) = 0.0003). The results were similar for European-Americans (OR(per allele) = 0.68; 95% CI: 0.54-0.86) and African-Americans (OR(per allele) = 0.61; 95% CI: 0.34-1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases OR(per allele) = 0.94; 95% CI: 0.79-1.11; localized, low-grade disease OR(per allele) = 0.98; 95% CI: 0.79-1.23; and aggressive disease OR(per allele) = 0.73; 95% CI: 0.50-1.07). CONCLUSION: These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype
— id: 134401, year: 2010, vol: 70, page: 646, stat: Journal Article,

Body mass index, cigarette smoking, and alcohol consumption and cancers of the oral cavity, pharynx, and larynx: modeling odds ratios in pooled case-control data
Lubin, Jay H; Gaudet, Mia M; Olshan, Andrew F; Kelsey, Karl; Boffetta, Paolo; Brennan, Paul; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Dal Maso, Luigino; Daudt, Alexander W; Fabianova, Eleonora; Fernandez, Leticia; Wunsch-Filho, Victor; Franceschi, Silvia; Herrero, Rolando; Koifman, Sergio; La Vecchia, Carlo; Lazarus, Philip; Levi, Fabio; Lissowska, Jolanta; Mates, Ioan Nicolae; Matos, Elena; McClean, Michael; Menezes, Ana; Morgenstern, Hal; Muscat, Joshua; Eluf Neto, Jose; Purdue, Mark P; Rudnai, Peter; Schwartz, Stephen M; Shangina, Oxana; Sturgis, Erich M; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Wei, Qingyi; Winn, Deborah; Zhang, Zuo-Feng; Hashibe, Mia; Hayes, Richard B
2010 Jun 15;171(12):1250-1261, American journal of epidemiology
Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer
— id: 139027, year: 2010, vol: 171, page: 1250, stat: Journal Article,

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk
Marron, Manuela; Boffetta, Paolo; Zhang, Zuo-Feng; Zaridze, David; Wunsch-Filho, Victor; Winn, Deborah M; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neonila; Sturgis, Erich M; Smith, Elaine; Schwartz, Stephen M; Rudnai, Peter; Purdue, Mark P; Olshan, Andrew F; Eluf-Neto, Jose; Muscat, Joshua; Morgenstern, Hal; Menezes, Ana; McClean, Michael; Matos, Elena; Mates, Ioan Nicolae; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; La Vecchia, Carlo; Koifman, Sergio; Kelsey, Karl; Herrero, Rolando; Hayes, Richard B; Franceschi, Silvia; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Dal Maso, Luigino; Curado, Maria Paula; Cadoni, Gabriella; Chen, Chu; Castellsague, Xavier; Boccia, Stefania; Benhamou, Simone; Ferro, Gilles; Berthiller, Julien; Brennan, Paul; Moller, Henrik; Hashibe, Mia
2010 Feb;39(1):182-196, International journal of epidemiology
BACKGROUND: Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. METHODS: We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. RESULTS: Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after > or =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after > or =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. CONCLUSIONS: Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer
— id: 134988, year: 2010, vol: 39, page: 182, stat: Journal Article,

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
McCullough, Marjorie L; Weinstein, Stephanie J; Freedman, D Michal; Helzlsouer, Kathy; Flanders, W Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Shu, Xiao-Ou
2010 Jul 1;172(1):21-35, American journal of epidemiology
Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes
— id: 132232, year: 2010, vol: 172, page: 21, stat: Journal Article,

The association of telomere length and genetic variation in telomere biology genes
Mirabello, Lisa; Yu, Kai; Kraft, Peter; De Vivo, Immaculata; Hunter, David J; Prescott, Jennifer; Wong, Jason Y Y; Chatterjee, Nilanjan; Hayes, Richard B; Savage, Sharon A
2010 Sep;31(9):1050-1058, Human mutation
Telomeres cap chromosome ends and are critical for genomic stability. Many telomere-associated proteins are important for telomere length maintenance. Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in genes encoding telomere-associated proteins (RTEL1 and TERT-CLPTM1) as markers of cancer risk. We conducted an association study of telomere length and 743 SNPs in 43 telomere biology genes. Telomere length in peripheral blood DNA was determined by Q-PCR in 3,646 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Nurses' Health Study. We investigated associations by SNP, gene, and pathway (functional group). We found no associations between telomere length and SNPs in TERT-CLPTM1L or RTEL1. Telomere length was not significantly associated with specific functional groups. Thirteen SNPs from four genes (MEN1, MRE11A, RECQL5, and TNKS) were significantly associated with telomere length. The strongest findings were in MEN1 (gene-based P=0.006), menin, which associates with the telomerase promoter and may negatively regulate telomerase. This large association study did not find strong associations with telomere length. The combination of limited diversity and evolutionary conservation suggest that these genes may be under selective pressure. More work is needed to explore the role of genetic variants in telomere length regulation
— id: 134415, year: 2010, vol: 31, page: 1050, stat: Journal Article,

Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey
Parekh, Niyati; Lin, Yong; Hayes, Richard B; Albu, Jeanine B; Lu-Yao, Grace L
2010 Apr;21(4):631-642, Cancer causes & control. ccc
Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994), with an average follow-up of 8.5 years to death, we evaluated markers of glucose and insulin metabolism, with cancer mortality, ascertained using death certificates or the National Death Index. Plasma glucose, insulin, C-peptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical, and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity, and body mass index, for every 50 mg/dl increase in plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI) (1.07-1.87; p = 0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin-resistant individuals (HR: 1.67; 95% CI: 1.15-2.42; p = 0.01), specifically among those with lower levels of physical activity (HR: 2.06; 95% CI: 1.4-3.0; p = 0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusion, hyperglycemia and insulin resistance may be 'high-risk' conditions for cancer mortality. Managing these conditions may be effective cancer control tools
— id: 133510, year: 2010, vol: 21, page: 631, stat: Journal Article,

A comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33
Parikh, Hemang; Deng, Zuoming; Yeager, Meredith; Boland, Joseph; Matthews, Casey; Jia, Jinping; Collins, Irene; White, Ariel; Burdett, Laura; Hutchinson, Amy; Qi, Liqun; Bacior, Jennifer A; Lonsberry, Victor; Rodesch, Matthew J; Jeddeloh, Jeffrey A; Albert, Thomas J; Halvensleben, Heather A; Harkins, Timothy T; Ahn, Jiyoung; Berndt, Sonja I; Chatterjee, Nilanjan; Hoover, Robert; Thomas, Gilles; Hunter, David J; Hayes, Richard B; Chanock, Stephen J; Amundadottir, Laufey
2010 Jan;127(1):91-99, Human genetics
Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF >1%) genetic variation in a 56 kb region on chromosome 19q13.33 centered on the KLK3 gene (chr19:56,019,829-56,076,043 bps). We identified 555 polymorphic loci in the process including 116 novel SNPs and 182 novel insertion/deletion polymorphisms (indels). Based on tagging analysis, 144 loci are necessary to tag the region at an r (2) threshold of 0.8 and MAF of 1% or higher, while 86 loci are required to tag the region at an r (2) threshold of 0.8 and MAF >5%. Our sequence data augments coverage by 35 and 78% as compared to variants in dbSNP and HapMap, respectively. We observed six non-synonymous amino acid or frame shift changes in the KLK3 gene and three changes in each of the neighboring genes, KLK15 and KLK2. Our study has generated a detailed map of common genetic variation in the genomic region surrounding the KLK3 gene, which should be useful for fine-mapping the association signal as well as determining the contribution of this locus to prostate cancer risk and/or regulation of PSA expression
— id: 103373, year: 2010, vol: 127, page: 91, stat: Journal Article,

Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2
Prokunina-Olsson, Ludmila; Fu, Yi-Ping; Tang, Wei; Jacobs, Kevin B; Hayes, Richard B; Kraft, Peter; Berndt, Sonja I; Wacholder, Sholom; Yu, Kai; Hutchinson, Amy; Spencer Feigelson, Heather; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Haiman, Christopher A; Henderson, Brian E; Kolonel, Laurence; Le Marchand, Loic; Siddiq, Afshan; Riboli, Elio; Travis, Ruth; Kaaks, Rudolf; Isaacs, William B; Isaacs, Sarah D; Gronberg, Henrik; Wiklund, Fredrik; Xu, Jianfeng; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Tucker, Margaret; Hoover, Robert N; Fraumeni, Joseph F Jr; Hunter, David J; Thomas, Gilles; Chatterjee, Nilanjan; Chanock, Stephen J; Yeager, Meredith
2010 May;19(5):1349-1355, Cancer epidemiology biomarkers & prevention
BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P=2.14x10(-6)), with a suggestion of stronger association with aggressive disease (P=1.2x10(-7)). METHODS: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry. RESULTS: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P=7.79x10(-11); ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P=1.60x10(-4) for aggressive cancer, n=4,597; P=3.25x10(-8) for nonaggressive cancer, n=4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P=0.587), body stature (rs849141, tagged by rs849136; P=0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P=0.657). CONCLUSION: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry. IMPACT: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa
— id: 139024, year: 2010, vol: 19, page: 1349, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of non-hodgkin lymphoma: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Purdue, Mark P; Freedman, D Michal; Gapstur, Susan M; Helzlsouer, Kathy J; Laden, Francine; Lim, Unhee; Maskarinec, Gertraud; Rothman, Nathaniel; Shu, Xiao-Ou; Stevens, Victoria L; Zeleniuch-Jacquotte, Anne; Albanes, Demetrius; Bertrand, Kimberly; Weinstein, Stephanie J; Yu, Kai; Irish, Lonn; Horst, Ronald L; Hoffman-Bolton, Judith; Giovannucci, Edward L; Kolonel, Laurence N; Snyder, Kirk; Willett, Walter; Arslan, Alan A; Hayes, Richard B; Zheng, Wei; Xiang, Yong-Bing; Hartge, Patricia
2010 Jul 1;172(1):58-69, American journal of epidemiology
Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (P(trend) = 0.68) or by sex (men, P(trend) = 0.50; women, P(trend) = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects
— id: 134378, year: 2010, vol: 172, page: 58, stat: Journal Article,

A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians
Schumacher, Fredrick R; Cheng, Iona; Freedman, Matthew L; Mucci, Lorelei; Allen, Naomi E; Pollak, Michael N; Hayes, Richard B; Stram, Daniel O; Canzian, Federico; Henderson, Brian E; Hunter, David J; Virtamo, Jarmo; Manjer, Jonas; Gaziano, J Michael; Kolonel, Laurence N; Tjonneland, Anne; Albanes, Demetrius; Calle, Eugenia E; Giovannucci, Edward; Crawford, E David; Haiman, Christopher A; Kraft, Peter; Willett, Walter C; Thun, Michael J; Le Marchand, Loic; Kaaks, Rudolf; Feigelson, Heather Spencer; Bueno-de-Mesquita, H Bas; Palli, Domenico; Riboli, Elio; Lund, Eiliv; Amiano, Pilar; Andriole, Gerald; Dunning, Alison M; Trichopoulos, Dimitrios; Stampfer, Meir J; Key, Timothy J; Ma, Jing
2010 Aug 1;19(15):3089-3101, Human molecular genetics
The insulin-like growth factor (IGF) pathway has been implicated in prostate development and carcinogenesis. We conducted a comprehensive analysis, utilizing a resequencing and tagging single-nucleotide polymorphism (SNP) approach, between common genetic variation in the IGF1, IGF binding protein (BP) 1, and IGFBP3 genes with IGF-I and IGFBP-3 blood levels, and prostate cancer (PCa) risk, among Caucasians in the NCI Breast and Prostate Cancer Cohort Consortium. We genotyped 14 IGF1 SNPs and 16 IGFBP1/IGFBP3 SNPs to capture common [minor allele frequency (MAF) >or= 5%] variation among Caucasians. For each SNP, we assessed the geometric mean difference in IGF blood levels (N = 5684) across genotypes and the association with PCa risk (6012 PCa cases/6641 controls). We present two-sided statistical tests and correct for multiple comparisons. A non-synonymous IGFBP3 SNP in exon 1, rs2854746 (Gly32Ala), was associated with IGFBP-3 blood levels (P(adj) = 8.8 x 10(-43)) after adjusting for the previously established IGFBP3 promoter polymorphism A-202C (rs2854744); IGFBP-3 blood levels were 6.3% higher for each minor allele. For IGF1 SNP rs4764695, the risk estimates among heterozygotes was 1.01 (99% CI: 0.90-1.14) and 1.20 (99% CI: 1.06-1.37) for variant homozygotes with overall PCa risk. The corrected allelic P-value was 8.7 x 10(-3). IGF-I levels were significantly associated with PCa risk (P(trend) = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile. We have identified SNPs significantly associated with IGFBP-3 blood levels, but none of these alter PCa risk; however, a novel IGF1 SNP, not associated with IGF-I blood levels, shows preliminary evidence for association with PCa risk among Caucasians
— id: 139026, year: 2010, vol: 19, page: 3089, stat: Journal Article,

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I; Monda, Keri L; Thorleifsson, Gudmar; Jackson, Anne U; Allen, Hana Lango; Lindgren, Cecilia M; Luan, Jian'an; Magi, Reedik; Randall, Joshua C; Vedantam, Sailaja; Winkler, Thomas W; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Weedon, Michael N; Wheeler, Eleanor; Wood, Andrew R; Ferreira, Teresa; Weyant, Robert J; Segre, Ayellet V; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpelainen, Tuomas O; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tonu; Feitosa, Mary F; Kutalik, Zoltan; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K; Absher, Devin M; Amin, Najaf; Dixon, Anna L; Fisher, Eva; Glazer, Nicole L; Goddard, Michael E; Heard-Costa, Nancy L; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F; Myers, Richard H; Narisu, Narisu; Perry, John R B; Peters, Marjolein J; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J; Timpson, Nicholas J; Tyrer, Jonathan P; van Wingerden, Sophie; Watanabe, Richard M; White, Charles C; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I; Cooper, Matthew N; Jansson, John-Olov; Lawrence, Robert W; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T S; Almgren, Peter; Arnold, Alice M; Aspelund, Thor; Atwood, Larry D; Balkau, Beverley; Balmforth, Anthony J; Bennett, Amanda J; Ben-Shlomo, Yoav; Bergman, Richard N; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I F; Boes, Tanja; Bonnycastle, Lori L; Bornstein, Stefan R; Brown, Morris J; Buchanan, Thomas A; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P; Cavalcanti-Proenca, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N M; Heijer, Martin den; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Facheris, Maurizio F; Felix, Stephan B; Fischer-Posovszky, Pamela; Folsom, Aaron R; Friedrich, Nele; Freimer, Nelson B; Fu, Mao; Gaget, Stefan; Gejman, Pablo V; Geus, Eco J C; Gieger, Christian; Gjesing, Anette P; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Grassler, Jurgen; Greenawalt, Danielle M; Groves, Christopher J; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S; Havulinna, Aki S; Hayward, Caroline; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jorgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W; Kolcic, Ivana; Konig, Inke R; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaloy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J; Lecoeur, Cecile; Lehtimaki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G; McArdle, Wendy L; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W; Morken, Mario A; Morris, Andrew P; Mulic, Rosanda; Ngwa, Julius S; Nelis, Mari; Neville, Matt J; Nyholt, Dale R; O'Donnell, Christopher J; O'Rahilly, Stephen; Ong, Ken K; Oostra, Ben; Pare, Guillaume; Parker, Alex N; Perola, Markus; Pichler, Irene; Pietilainen, Kirsi H; Platou, Carl G P; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W; Ridderstrale, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R; Sandhu, Manjinder S; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S; Smit, Jan H; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M; Thompson, John R; Thomson, Brian; Tonjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B J; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I G; Voight, Benjamin F; Waite, Lindsay L; Wallaschofski, Henri; Walters, G Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H; Willemsen, Gonneke; Witte, Daniel R; Witteman, Jacqueline C; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P; Farooqi, I Sadaf; Hebebrand, Johannes; Huikuri, Heikki V; James, Alan L; Kahonen, Mika; Levinson, Douglas F; Macciardi, Fabio; Nieminen, Markku S; Ohlsson, Claes; Palmer, Lyle J; Ridker, Paul M; Stumvoll, Michael; Beckmann, Jacques S; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I; Caulfield, Mark J; Chanock, Stephen J; Collins, Francis S; Cupples, L Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Gronberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B; Hattersley, Andrew T; Hayes, Richard B; Heinrich, Joachim; Hu, Frank B; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A; Metspalu, Andres; Munroe, Patricia B; Ouwehand, Willem H; Pedersen, Oluf; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J; Schwarz, Peter E H; Shuldiner, Alan R; Spector, Timothy D; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, Andre; Valle, Timo T; Wabitsch, Martin; Waeber, Gerard; Wareham, Nicholas J; Watkins, Hugh; Wilson, James F; Wright, Alan F; Zillikens, M Carola; Chatterjee, Nilanjan; McCarroll, Steven A; Purcell, Shaun; Schadt, Eric E; Visscher, Peter M; Assimes, Themistocles L; Borecki, Ingrid B; Deloukas, Panos; Fox, Caroline S; Groop, Leif C; Haritunians, Talin; Hunter, David J; Kaplan, Robert C; Mohlke, Karen L; O'Connell, Jeffrey R; Peltonen, Leena; Schlessinger, David; Strachan, David P; van Duijn, Cornelia M; Wichmann, H-Erich; Frayling, Timothy M; Thorsteinsdottir, Unnur; Abecasis, Goncalo R; Barroso, Ines; Boehnke, Michael; Stefansson, Kari; North, Kari E; McCarthy, Mark I; Hirschhorn, Joel N; Ingelsson, Erik; Loos, Ruth J F
2010 Nov;42(11):937-948, Nature genetics
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and approximately 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation
— id: 114368, year: 2010, vol: 42, page: 937, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N
2010 Jul 1;172(1):81-93, American journal of epidemiology
Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered
— id: 134377, year: 2010, vol: 172, page: 81, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Zeleniuch-Jacquotte, Anne; Gallicchio, Lisa; Hartmuller, Virginia; Helzlsouer, Kathy J; McCullough, Marjorie L; Setiawan, V Wendy; Shu, Xiao-Ou; Weinstein, Stephanie J; Weiss, Jocelyn M; Arslan, Alan A; De Vivo, Immaculata; Gao, Yu-Tang; Hayes, Richard B; Henderson, Brian E; Horst, Ronald L; Koenig, Karen L; Patel, Alpa V; Purdue, Mark P; Snyder, Kirk; Steplowski, Emily; Yu, Kai; Zheng, Wei; Hankinson, Susan E
2010 Jul 1;172(1):36-46, American journal of epidemiology
A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50-<75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the <25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the > or =100 nmol/L category (P(trend) = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was > or =100 nmol/L, and for stratified analyses, > or =75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer
— id: 110661, year: 2010, vol: 172, page: 36, stat: Journal Article,

Occupational exposure to formaldehyde, hematotoxicity, and leukemia-specific chromosome changes in cultured myeloid progenitor cells
Zhang, Luoping; Tang, Xiaojiang; Rothman, Nathaniel; Vermeulen, Roel; Ji, Zhiying; Shen, Min; Qiu, Chuangyi; Guo, Weihong; Liu, Songwang; Reiss, Boris; Freeman, Laura Beane; Ge, Yichen; Hubbard, Alan E; Hua, Ming; Blair, Aaron; Galvan, Noe; Ruan, Xiaolin; Alter, Blanche P; Xin, Kerry X; Li, Senhua; Moore, Lee E; Kim, Sungkyoon; Xie, Yuxuan; Hayes, Richard B; Azuma, Mariko; Hauptmann, Michael; Xiong, Jun; Stewart, Patricia; Li, Laiyu; Rappaport, Stephen M; Huang, Hanlin; Fraumeni, Joseph F Jr; Smith, Martyn T; Lan, Qing
2010 Jan;19(1):80-88, Cancer epidemiology biomarkers & prevention
There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing, and other industries. Epidemiologic studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on the ability of formaldehyde to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures
— id: 139021, year: 2010, vol: 19, page: 80, stat: Journal Article,

Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Zheng, Wei; Danforth, Kim N; Tworoger, Shelley S; Goodman, Marc T; Arslan, Alan A; Patel, Alpa V; McCullough, Marjorie L; Weinstein, Stephanie J; Kolonel, Laurence N; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Steplowski, Emily; Visvanathan, Kala; Yu, Kai; Zeleniuch-Jacquotte, Anne; Gao, Yu-Tang; Hankinson, Susan E; Harvey, Chinonye; Hayes, Richard B; Henderson, Brian E; Horst, Ronald L; Helzlsouer, Kathy J
2010 Jul 1;172(1):70-80, American journal of epidemiology
A role for vitamin D in ovarian cancer etiology is supported by ecologic studies of sunlight exposure, experimental mechanism studies, and some studies of dietary vitamin D intake and genetic polymorphisms in the vitamin D receptor. However, few studies have examined the association of circulating 25-hydroxyvitamin D (25(OH)D), an integrated measure of vitamin D status, with ovarian cancer risk. A nested case-control study was conducted among 7 prospective studies to evaluate the circulating 25(OH)D concentration in relation to epithelial ovarian cancer risk. Logistic regression models were used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls. Compared with 25(OH)D concentrations of 50-<75 nmol/L, no statistically significant associations were observed for <37.5 (odds ratio (OR) = 1.21, 95% confidence interval (CI): 0.87, 1.70), 37.5-<50 (OR = 1.03, 95% CI: 0.75, 1.41), or > or =75 (OR = 1.11, 95% CI: 0.79, 1.55) nmol/L. Analyses stratified by tumor subtype, age, body mass index, and other variables were generally null but suggested an inverse association between 25(OH)D and ovarian cancer risk among women with a body mass index of > or =25 kg/m(2) (P(interaction) < 0.01). In conclusion, this large pooled analysis did not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women
— id: 134376, year: 2010, vol: 172, page: 70, stat: Journal Article,

Height and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial
Ahn, J; Moore, S C; Albanes, D; Huang, W-Y; Leitzmann, M F; Hayes, R B
2009 Aug 4;101(3):522-525, British journal of cancer
Background:The relationship between prostate cancer and height is uncertain.Methods:We prospectively examined the association of height with prostate cancer among 34268 men in the prostate, lung, colorectal, and ovarian cancer trial. Anthropometry was assessed at baseline and 2144 incident prostate cancer cases were identified upto 8.9 years of follow-up.Results:Overall, tallness was not associated with the risk of prostate cancer or with the risk of non-aggressive disease, but the risk for aggressive prostate cancer tended to be greater in taller men (Gleason score >/=7 or stage >/=III; P trend=0.05; relative risk (RR) for 190 cm+ vs </=170 cm=1.39, 95% confidence interval (95% CI): 0.96-2.01). This association was largely limited to men below the age of 65 years (P trend=0.008; RR for 190 cm+ vs </=170 cm=1.76, 95% CI: 1.06-2.93; P for interaction=0.009), although the number of cases was small and risk estimates were somewhat unstable.Conclusion:The results of this large prospective prostate cancer screening trial suggest that tallness is associated with increased risk for younger onset aggressive prostate cancer.British Journal of Cancer advance online publication, 30 June 2009; doi:10.1038/sj.bjc.6605159 www.bjcancer.com
— id: 100577, year: 2009, vol: 101, page: 522, stat: Journal Article,

Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk
Ahn, Jiyoung; Albanes, Demetrius; Berndt, Sonja I; Peters, Ulrike; Chatterjee, Nilanjan; Freedman, Neal D; Abnet, Christian C; Huang, Wen-Yi; Kibel, Adam S; Crawford, E David; Weinstein, Stephanie J; Chanock, Stephen J; Schatzkin, Arthur; Hayes, Richard B
2009 May;30(5):769-776, Carcinogenesis
We systematically investigated the association of 48 SNPS in four vitamin D metabolizing genes [CYP27A1, GC, CYP27B1 and CYP24A1] with serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels and the association of these SNPS and an additional 164 SNPS in eight downstream mediators of vitamin D signaling [VDR, RXRA, RXRB, PPAR, NCOA1, NCOA2, NCOA3 and SMAD3] with prostate cancer risk in the 749 incident prostate cancer cases and 781 controls of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. 25(OH)D (all cases and controls) and 1,25(OH)(2)D (a subset of 150 controls) levels were measured by radioimmunoassay and SNP data were genotyped as part of a genome-wide scan. Among investigated SNPS, only four tag SNPS in GC, the major serum 25(OH)D carrier, were associated with 25(OH)D levels; no SNPS were associated with 1,25(OH)(2)D levels. None of the 212 SNPS examined were associated with cancer risk overall. Among men in the lowest tertile of serum 25(OH)D (<48.9 nmol/l), however, prostate cancer risk was related to tag SNPS in or near the 3' untranslated region (UTR) of VDR, with the strongest association for rs11574143 [odds ratio (95% confidence interval) for risk allele carriers versus wild-type: 2.49 (1.51-4.11), P = 0.0007]; the genotype associations were null among men in tertile 2 and tertile 3. Results from the most comprehensive evaluation of serum vitamin D and its related genes to date suggest that tag SNPS in the 3' UTR of VDR may be associated with risk of prostate cancer in men with low vitamin D status
— id: 98934, year: 2009, vol: 30, page: 769, stat: Journal Article,

Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)
Ahn, Jiyoung; Schumacher, Fredrick R; Berndt, Sonja I; Pfeiffer, Ruth; Albanes, Demetrius; Andriole, Gerald L; Ardanaz, Eva; Boeing, Heiner; Bueno-de-Mesquita, Bas; Chanock, Stephen J; Clavel-Chapelon, Francoise; Diver, W Ryan; Feigelson, Heather Spencer; Gaziano, J Michael; Giovannucci, Edward; Haiman, Christopher A; Henderson, Brian E; Hoover, Robert N; Kolonel, Laurence N; Kraft, Peter; Ma, Jing; Le Marchand, Loic; Overvad, Kim; Palli, Domenico; Stattin, Par; Stampfer, Meir; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Travis, Ruth C; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J; Yeager, Meredith; Kaaks, Rudolf; Hunter, David J; Hayes, Richard B
2009 Oct 1;18(19):3749-3757, Human molecular genetics
Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N=4,720), testosterone (N=4,678), 3alpha-androstanediol-glucuronide (N=4,767), and 17beta-estradiol (N=2,014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (p=4.52x10(-21)), consistent with previous studies, and testosterone (p=7.54x10(-15)), with mean difference of 26.9% and 14.3% respectively, comparing wildtype to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference=8.8%, p=7.37x10(-6)) and SRD5A2 with 3alpha-androstanediol-glucuronide (rs2208532, mean difference=11.8%, p=1.82x10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones
— id: 100576, year: 2009, vol: 18, page: 3749, stat: Journal Article,

SLC6A3 and body mass index in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
Azzato, Elizabeth M; Morton, Lindsay M; Bergen, Andrew W; Wang, Sophia S; Chatterjee, Nilanjan; Kvale, Paul; Yeager, Meredith; Hayes, Richard B; Chanock, Stephen J; Caporaso, Neil E
2009 ;10:9-9, BMC medical genetics
BACKGROUND: To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(SLC6A3) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. METHODS: Four polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR) polymorphism) at the SLC6A3 gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5-24.9, 25.0-29.9, or > or = 30 kg/m2, respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of SLC6A3 genotypes and haplotypes were computed using conditional logistic regression. RESULTS: Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the 3' VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR*9 = 0.80, OR99 = 0.47, Ptrend = 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; ORA-C-G-9 = 0.80, 95% CI 0.65-0.99, p = 0.04) and obese individuals (A-C-G-* is referent; ORA-C-G-9 = 0.70, 95% CI 0.49-0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9). CONCLUSION: Our results support a role of genetic variation at the dopamine transporter gene, SLC6A3, as a modifier of BMI
— id: 139006, year: 2009, vol: 10, page: 9, stat: Journal Article,

Genetic variants in frizzled-related protein (FRZB) and the risk of colorectal neoplasia
Berndt, Sonja I; Huang, Wen-Yi; Yeager, Meredith; Weissfeld, Joel L; Chanock, Stephen J; Hayes, Richard B
2009 May;20(4):487-490, Cancer causes & control. ccc
OBJECTIVE: The Wnt/APC/beta-catenin signaling pathway, which includes frizzled-related protein (FRZB), plays a critical role in the development of colorectal cancer, and recent evidence suggests that the functional polymorphism, FRZB Arg324Gly, may be associated with risk for this disease. To determine if this finding could be replicated, we investigated the association between two FRZB polymorphisms (Arg324Gly and Arg200Trp) and the risk of colorectal adenoma and cancer in nested case-control studies. METHODS: Participants consisted of 1,709 adenoma cases, 620 cancer cases, and 1,849 controls within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations with colorectal neoplasia. RESULTS: No association was observed for either polymorphism or any haplotypes with colorectal adenoma or colorectal cancer (p > 0.05 for all). CONCLUSION: Our study does not support the previously observed association between the FRZB 324Gly variant and colorectal cancer risk. However, further study of additional genetic variants within this pathway is still warranted, given the important role of the Wnt signaling pathway in colorectal carcinogenesis
— id: 91730, year: 2009, vol: 20, page: 487, stat: Journal Article,

Xenobiotic Metabolizing Genes, Meat Intake, and Risk of Advanced Colorectal Adenoma
Ferrucci, LM; Cross, AJ; Gunter, MJ; Ahn, J; Mayne, ST; Ma, XM; Chanock, SJ; Yeager, M; Graubard, BI; Berndt, SI; Huang, WY; Hayes, RB; Sinha, R
2009 AUG ;2(4-5):194-194, Journal of nutrigenetics & nutrigenomics
— id: 110118, year: 2009, vol: 2, page: 194, stat: Journal Article,

Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium
Hashibe, Mia; Brennan, Paul; Chuang, Shu-Chun; Boccia, Stefania; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Dal Maso, Luigino; Daudt, Alexander W; Fabianova, Eleonora; Fernandez, Leticia; Wunsch-Filho, Victor; Franceschi, Silvia; Hayes, Richard B; Herrero, Rolando; Kelsey, Karl; Koifman, Sergio; La Vecchia, Carlo; Lazarus, Philip; Levi, Fabio; Lence, Juan J; Mates, Dana; Matos, Elena; Menezes, Ana; McClean, Michael D; Muscat, Joshua; Eluf-Neto, Jose; Olshan, Andrew F; Purdue, Mark; Rudnai, Peter; Schwartz, Stephen M; Smith, Elaine; Sturgis, Erich M; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Wei, Qingyi; Winn, Deborah M; Shangina, Oxana; Pilarska, Agnieszka; Zhang, Zuo-Feng; Ferro, Gilles; Berthiller, Julien; Boffetta, Paolo
2009 Feb;18(2):541-550, Cancer epidemiology biomarkers & prevention
BACKGROUND: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. METHODS: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). RESULTS: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). CONCLUSIONS: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases
— id: 139007, year: 2009, vol: 18, page: 541, stat: Journal Article,

Mortality from lymphohematopoietic malignancies and brain cancer among embalmers exposed to formaldehyde
Hauptmann, Michael; Stewart, Patricia A; Lubin, Jay H; Beane Freeman, Laura E; Hornung, Richard W; Herrick, Robert F; Hoover, Robert N; Fraumeni, Joseph F Jr; Blair, Aaron; Hayes, Richard B
2009 Dec 16;101(24):1696-1708, Journal of the National Cancer Institute
BACKGROUND: Excess mortality from lymphohematopoietic malignancies, in particular myeloid leukemia, and brain cancer has been found in surveys of anatomists, pathologists, and funeral industry workers, all of whom may have worked with formaldehyde. We investigated the relation of mortality to work practices and formaldehyde exposure levels among these professionals to address cancer risk in the funeral industry. METHODS: Professionals employed in the funeral industry who died between January 1, 1960, and January 1, 1986, from lymphohematopoietic malignancies (n = 168) or brain tumors (n = 48) (ie, case subjects) were compared with deceased matched control subjects (n = 265) with regard to lifetime work practices and exposures in the funeral industry, which were obtained by interviews with next of kin and coworkers, and to estimated levels of formaldehyde exposure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by use of logistic regression. All statistical tests were two-sided. RESULTS: Mortality from myeloid leukemia increased statistically significantly with increasing number of years of embalming (P for trend = .020) and with increasing peak formaldehyde exposure (P for trend = .036). Compared with subjects who performed fewer than 500 lifetime embalmings, mortality from myeloid leukemia was elevated among those who performed embalmings for more than 34 years (OR = 3.9, 95% CI = 1.2 to 12.5, P = .024), who performed more than 3068 embalmings (OR = 3.0, 95% CI = 1.0 to 9.2, P = .057), and those whose estimated cumulative formaldehyde exposure exceeded 9253 parts per million-hours (OR = 3.1; 95% CI = 1.0 to 9.6, P = .047). These exposures were not related to other lymphohematopoietic malignancies or to brain cancer. CONCLUSION: Duration of embalming practice and related formaldehyde exposures in the funeral industry were associated with statistically significantly increased risk for mortality from myeloid leukemia
— id: 139018, year: 2009, vol: 101, page: 1696, stat: Journal Article,

Xenobiotic metabolizing gene variants, dietary heterocyclic amine intake, and risk of prostate cancer
Koutros, Stella; Berndt, Sonja I; Sinha, Rashmi; Ma, Xiaomei; Chatterjee, Nilanjan; Alavanja, Michael C R; Zheng, Tongzhang; Huang, Wen-Yi; Hayes, Richard B; Cross, Amanda J
2009 Mar 1;69(5):1877-1884, Cancer research
We recently reported that heterocyclic amines (HCA) are associated with prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We now use extensive genetic data from this resource to determine if risks associated with dietary HCAs {2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx); and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)} from cooked meat are modified by single nucleotide polymorphisms (SNP) in genes involved in HCA metabolism (CYP1A1, CYP1A2, CYP1B1, GSTA1, GSTM1, GSTM3, GSTP1, NAT1, NAT2, SULT1A1, SULT1A2, and UGT1A locus). We conducted a nested case-control study that included 1,126 prostate cancer cases and 1,127 controls selected for a genome-wide association study for prostate cancer. Unconditional logistic regression was used to estimate odds ratios (OR), 95% confidence intervals (95% CI), and P values for the interaction between SNPs, HCA intake, and risk of prostate cancer. The strongest evidence for an interaction was noted between DiMeIQx and MeIQx and the polymorphism rs11102001 downstream of the GSTM3 locus (P(interaction) = 0.001 for both HCAs; statistically significant after correction for multiple testing). Among men carrying the A variant, the risk of prostate cancer associated with high DiMeIQx intake was 2-fold greater than that with low intake (OR, 2.3; 95% CI, 1.2-4.7). The SNP rs11102001, which encodes a nonsynonymous amino acid change P356S in EPS8L3, is a potential candidate modifier of the effect of HCAs on prostate cancer risk. The observed effect provides evidence to support the hypothesis that HCAs may act as promoters of malignant transformation by altering mitogenic signaling
— id: 139009, year: 2009, vol: 69, page: 1877, stat: Journal Article,

Beyond odds ratios--communicating disease risk based on genetic profiles
Kraft, Peter; Wacholder, Sholom; Cornelis, Marilyn C; Hu, Frank B; Hayes, Richard B; Thomas, Gilles; Hoover, Robert; Hunter, David J; Chanock, Stephen
2009 Apr;10(4):264-269, Nature reviews. Genetics
The brisk discovery of novel inherited disease markers by genome-wide association (GWA) studies has raised expectations for predicting disease risk by analysing multiple common alleles. However, the statistics used during the discovery phase of research (such as odds ratios or p values for association) are not the most appropriate measures for evaluating the predictive value of genetic profiles. We argue that other measures--such as sensitivity, specificity, and positive and negative predictive values--are more useful when proposing a genetic profile for risk prediction
— id: 139010, year: 2009, vol: 10, page: 264, stat: Journal Article,

Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity
Lan, Qing; Zhang, Luoping; Shen, Min; Jo, William J; Vermeulen, Roel; Li, Guilan; Vulpe, Christopher; Lim, Sophia; Ren, Xuefeng; Rappaport, Stephen M; Berndt, Sonja I; Yeager, Meredith; Yuenger, Jeff; Hayes, Richard B; Linet, Martha; Yin, Songnian; Chanock, Stephen; Smith, Martyn T; Rothman, Nathaniel
2009 Jan;30(1):50-58, Carcinogenesis
Benzene is an established human hematotoxicant and leukemogen but its mechanism of action is unclear. To investigate the role of single-nucleotide polymorphisms (SNPs) on benzene-induced hematotoxicity, we analyzed 1395 SNPs in 411 genes using an Illumina GoldenGate assay in 250 benzene-exposed workers and 140 unexposed controls. Highly significant findings clustered in five genes (BLM, TP53, RAD51, WDR79 and WRN) that play a critical role in DNA repair and genomic maintenance, and these regions were then further investigated with tagSNPs. One or more SNPs in each gene were associated with highly significant 10-20% reductions (P values ranged from 0.0011 to 0.0002) in the white blood cell (WBC) count among benzene-exposed workers but not controls, with evidence for gene-environment interactions for SNPs in BLM, WRN and RAD51. Further, among workers exposed to benzene, the genotype-associated risk of having a WBC count <4000 cells/microl increased when using individuals with progressively higher WBC counts as the comparison group, with some odds ratios >8-fold. In vitro functional studies revealed that deletion of SGS1 in yeast, equivalent to lacking BLM and WRN function in humans, caused reduced cellular growth in the presence of the toxic benzene metabolite hydroquinone, and knockdown of WRN using specific short hairpin RNA increased susceptibility of human TK6 cells to hydroquinone toxicity. Our findings suggest that SNPs involved in DNA repair and genomic maintenance, with particular clustering in the homologous DNA recombination pathway, play an important role in benzene-induced hematotoxicity
— id: 91726, year: 2009, vol: 30, page: 50, stat: Journal Article,

B-cell clones as early markers for chronic lymphocytic leukemia
Landgren, Ola; Albitar, Maher; Ma, Wanlong; Abbasi, Fatima; Hayes, Richard B; Ghia, Paolo; Marti, Gerald E; Caporaso, Neil E
2009 Feb 12;360(7):659-667, New England journal of medicine
BACKGROUND: Otherwise healthy persons with a small number of B-cell clones circulating in the peripheral blood have been designated as having monoclonal B-cell lymphocytosis (MBL). Hospital-based series indicate an excess risk of progression from MBL to chronic lymphocytic leukemia (CLL). In this prospective cohort study, we tested the hypothesis that CLL is always preceded by MBL. METHODS: Among 77,469 healthy adults who were enrolled in the nationwide, population-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 45 subjects in whom CLL was subsequently diagnosed (up to 6.4 years later) through the collection of a peripheral-blood sample. Using six-color flow cytometry (with antibodies CD45, CD19, CD5, CD10, kappa, and lambda) and immunoglobulin heavy-chain gene rearrangement by reverse-transcriptase-polymerase-chain-reaction assay, we determined the association between MBL and subsequent CLL and characterized the immunoglobulin gene repertoire of the prediagnostic B-cell clones. RESULTS: On the basis of either flow-cytometric or molecular analysis, 44 of 45 patients with CLL (98%; 95% confidence interval [CI], 88 to 100) had a prediagnostic B-cell clone; in 41 patients (91%; 95% CI, 79 to 98), the presence of the B-cell clone was confirmed by both methods. The presence of immunoglobulin heavy-chain variable (IGHV) genes was determined in 35 of 45 prediagnostic clones (78%). Of these clones, 16 (46%) were IGHV3 subgroup genes (including 6 [17%] IGHV3-23 genes) and 9 (26%) were IGHV4 subgroup genes (including 4 [11%] IGHV4-34 genes). Furthermore, 27 of 35 of the IGHV sequences (77%) had mutations, with similar distributions after stratification either below or above the median time between the collection of the prediagnostic blood sample and the subsequent CLL diagnosis. CONCLUSIONS: In peripheral blood obtained up to 77 months before a CLL diagnosis, prediagnostic B-cell clones were present in 44 of 45 patients with CLL
— id: 139008, year: 2009, vol: 360, page: 659, stat: Journal Article,

Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study
Landgren, Ola; Kyle, Robert A; Pfeiffer, Ruth M; Katzmann, Jerry A; Caporaso, Neil E; Hayes, Richard B; Dispenzieri, Angela; Kumar, Shaji; Clark, Raynell J; Baris, Dalsu; Hoover, Robert; Rajkumar, S Vincent
2009 May 28;113(22):5412-5417, Blood
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77,469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)-proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS
— id: 139005, year: 2009, vol: 113, page: 5412, stat: Journal Article,

Nitric oxide synthase gene polymorphisms and prostate cancer risk
Lee, Kyoung-Mu; Kang, Daehee; Park, Sue Kyung; Berndt, Sonja I; Reding, Douglas; Chatterjee, Nilanjan; Chanock, Stephen; Huang, Wen-Yi; Hayes, Richard B
2009 Apr;30(4):621-625, Carcinogenesis
Nitric oxide (NO) induces cytotoxicity and angiogenesis, and may play a role in prostate carcinogenesis, potentially modulated by environmental exposures. We evaluated the association of prostate cancer with genetic polymorphisms in two genes related to intracellular NO: NOS2A [i-NOS; -2892T>C, Ex16+14C>T (S608L), IVS16+88T>G, and IVS20+524G>A] and NOS3 [e-NOS; IVS1-762C>T, Ex7-43C>T (D258D), IVS7-26A>G, Ex8-63G>T (E298D), and IVS15-62G>T]. Prostate cancer cases (n=1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were frequency-matched to controls (n=1,842), by age, race, time since initial screening, and year of blood draw. An antioxidant score (range 3-12; low [3-7] vs. high [8-12]) was created by summing the quartile levels of vitamin E, beta-carotene, and lycopene, which were coded from 1 to 4, respectively. The global tests for all 8 SNPs (excluding NOS2 -2892T>C, with low minor allele frequency) were statistically significant for prostate cancer (P=0.005), especially for aggressive cancer (Stage III-IV or Gleason score>/=7) (P=0.01). The NOS2A IVS16+88 GT/TT was associated with increased prostate caner risk (OR=1.24, 95% CI=1.00-1.54), whereas the IVS20+524 AG/GG was associated with decreased risk (0.77, 0.66-0.90). The NOS3 IVS7-26 GG was associated with increased prostate caner risk (1.33, 1.07-1.64). All these SNPs showed significant associations with aggressive cancer and not for non-aggressive cancer. In the evaluation of effect modification, the effect of the NOS2A IVS16+88 GT/TT on aggressive cancer was stronger among subjects with higher antioxidant intake (1.61, 1.18-2.19; P(interaction)=0.01). Our results suggest that NOS gene polymorphisms are genetic susceptibility factors for aggressive prostate cancer
— id: 91733, year: 2009, vol: 30, page: 621, stat: Journal Article,

Fine mapping and functional analysis of a common variant in MSMB on chromosome 10q11.2 associated with prostate cancer susceptibility
Lou, Hong; Yeager, Meredith; Li, Hongchuan; Bosquet, Jesus Gonzalez; Hayes, Richard B; Orr, Nick; Yu, Kai; Hutchinson, Amy; Jacobs, Kevin B; Kraft, Peter; Wacholder, Sholom; Chatterjee, Nilanjan; Feigelson, Heather Spencer; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Ma, Jing; Gaziano, J Michael; Stampfer, Meir; Schumacher, Fredrick R; Giovannucci, Edward; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Anderson, Stephen K; Tucker, Margaret; Hoover, Robert N; Fraumeni, Joseph F Jr; Thomas, Gilles; Hunter, David J; Dean, Michael; Chanock, Stephen J
2009 May 12;106(19):7933-7938, Proceedings of the National Academy of Sciences of the United States of America
Two recent genome-wide association studies have independently identified a prostate cancer susceptibility locus on chromosome 10q11.2. The most significant single-nucleotide polymorphism (SNP) marker reported, rs10993994, is 57 bp centromeric of the first exon of the MSMB gene, which encodes beta-microseminoprotein (prostatic secretory protein 94). In this study, a fine-mapping analysis using HapMap SNPs was conducted across a approximately 65-kb region (chr10: 51168330-51234020) flanking rs10993994 with 13 tag SNPs in 6,118 prostate cancer cases and 6,105 controls of European origin from the Cancer Genetic Markers of Susceptibility (CGEMS) project. rs10993994 remained the most strongly associated marker with prostate cancer risk [P = 8.8 x 10(-18); heterozygous odds ratio (OR) = 1.20, 95% confidence interval (CI): 1.11-1.30; homozygous OR = 1.64, 95% CI: 1.47-1.86 for the adjusted genotype test with 2 df]. In follow-up functional analyses, the T variant of rs10993994 significantly affected expression of in vitro luciferase reporter constructs. In electrophoretic mobility shift assays, the C allele of rs10993994 preferentially binds to the CREB transcription factor. Analysis of tumor cell lines with a CC or CT genotype revealed a high level of MSMB gene expression compared with cell lines with a TT genotype. These findings were specific to the alleles of rs10993994 and were not observed for other SNPs determined by sequence analysis of the proximal promoter. Together, our mapping study and functional analyses implicate regulation of expression of MSMB as a plausible mechanism accounting for the association identified at this locus. Further investigation is warranted to determine whether rs10993994 alone or in combination with additional variants contributes to prostate cancer susceptibility
— id: 139012, year: 2009, vol: 106, page: 7933, stat: Journal Article,

Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies
Lubin, Jay H; Purdue, Mark; Kelsey, Karl; Zhang, Zuo-Feng; Winn, Debbie; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neonilia; Sturgis, Erich M; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M; Rudnai, Peter; Neto, Jose Eluf; Muscat, Joshua; Morgenstern, Hal; Menezes, Ana; Matos, Elena; Mates, Ioan Nicolae; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; La Vecchia, Carlo; Koifman, Sergio; Herrero, Rolando; Franceschi, Silvia; Wunsch-Filho, Victor; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Maso, Luigino Dal; Curado, Maria Paula; Chen, Chu; Castellsague, Xavier; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia; Hayes, Richard B
2009 Oct 15;170(8):937-947, American journal of epidemiology
Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day
— id: 139015, year: 2009, vol: 170, page: 937, stat: Journal Article,

Family history of cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium
Negri, Eva; Boffetta, Paolo; Berthiller, Julien; Castellsague, Xavier; Curado, Maria Paula; Dal Maso, Luigino; Daudt, Alexander W; Fabianova, Eleonora; Fernandez, Leticia; Wunsch-Filho, Victor; Franceschi, Silvia; Hayes, Richard B; Herrero, Rolando; Koifman, Sergio; Lazarus, Philip; Lence, Juan J; Levi, Fabio; Mates, Dana; Matos, Elena; Menezes, Ana; Muscat, Joshua; Eluf-Neto, Jose; Olshan, Andrew F; Rudnai, Peter; Shangina, Oxana; Sturgis, Erich M; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Wei, Qingyi; Winn, Deborah M; Zaridze, David; Lissowska, Jolanta; Zhang, Zuo-Feng; Ferro, Gilles; Brennan, Paul; La Vecchia, Carlo; Hashibe, Mia
2009 Jan 15;124(2):394-401, International journal of cancer
Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather than a parent (OR=1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC
— id: 91724, year: 2009, vol: 124, page: 394, stat: Journal Article,

Type of alcoholic beverage and risk of head and neck cancer--a pooled analysis within the INHANCE Consortium
Purdue, Mark P; Hashibe, Mia; Berthiller, Julien; La Vecchia, Carlo; Dal Maso, Luigino; Herrero, Rolando; Franceschi, Silvia; Castellsague, Xavier; Wei, Qingyi; Sturgis, Erich M; Morgenstern, Hal; Zhang, Zuo-Feng; Levi, Fabio; Talamini, Renato; Smith, Elaine; Muscat, Joshua; Lazarus, Philip; Schwartz, Stephen M; Chen, Chu; Neto, Jose Eluf; Wunsch-Filho, Victor; Zaridze, David; Koifman, Sergio; Curado, Maria Paula; Benhamou, Simone; Matos, Elena; Szeszenia-Dabrowska, Neonilia; Olshan, Andrew F; Lence, Juan; Menezes, Ana; Daudt, Alexander W; Mates, Ioan Nicolae; Pilarska, Agnieszka; Fabianova, Eleonora; Rudnai, Peter; Winn, Debbie; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hayes, Richard B
2009 Jan 15;169(2):132-142, American journal of epidemiology
The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for < or =5, 6-15, 16-30, and >30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution
— id: 91729, year: 2009, vol: 169, page: 132, stat: Journal Article,

Serum retinol and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial
Schenk, Jeannette M; Riboli, Elio; Chatterjee, Nilanjan; Leitzmann, Michael F; Ahn, Jiyoung; Albanes, Demetrius; Reding, Douglas J; Wang, Yinghui; Friesen, Marlin D; Hayes, Richard B; Peters, Ulrike
2009 Apr;18(4):1227-1231, Cancer epidemiology biomarkers & prevention
Vitamin A (retinol) plays a key role in the regulation of cell growth and differentiation, and has been studied as a potential chemopreventive agent for prostate cancer. However, findings from epidemiologic studies on the association between circulating retinol concentrations and the risk of prostate cancer are inconsistent. We examined whether serum concentrations of retinol were associated with the risk of prostate cancer in a nested case-control study using 692 prostate cancer cases and 844 matched controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We estimated the risk of prostate cancer using multivariate, conditional logistic regression to calculate odds ratios and 95% confidence intervals for overall prostate cancer and aggressive disease (stage III or IV or Gleason >7; n = 269). Serum retinol concentrations were not associated with overall prostate cancer risk; however, the highest versus lowest concentrations of serum retinol were associated with a 42% reduction in aggressive prostate cancer risk (P(trend) = 0.02), with the strongest inverse association for high-grade disease (Gleason sum >7; odds ratio, 0.52; 95% confidence interval, 0.32-0.84; P(trend) = 0.01). Our results suggest that higher circulating concentrations of retinol are associated with a decreased risk of aggressive prostate cancer. Further research is needed to better understand the significance of elevations in serum retinol concentrations and the possible biological mechanisms through which retinol affects prostate cancer
— id: 98933, year: 2009, vol: 18, page: 1227, stat: Journal Article,

HNF1B and JAZF1 genes, diabetes, and prostate cancer risk
Stevens, Victoria L; Ahn, Jiyoung; Sun, Juzhong; Jacobs, Eric J; Moore, Steven C; Patel, Alpa V; Berndt, Sonja I; Albanes, Demetrius; Hayes, Richard B
2009 Dec 8;70(6):601-607, Prostate
BACKGROUND: Epidemiologic studies have shown that men with type II diabetes have a lower risk of prostate cancer than non-diabetic men. Recently, common variants in two genes, HNF1B and JAZF1, were found to be associated with both of these diseases. METHODS: We examined whether the relationship between HNF1B and JAZF1 variants and decreased prostate cancer risk may potentially be mediated through diabetes in two large prospective studies, the Cancer Prevention Study II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. RESULTS: Three HNF1B SNPS, rs11649743, rs4430796, and rs7501939, were associated with decreased risk of prostate cancer and were also associated, with marginal statistical significance, with increased risk of diabetes. The JAZF1 SNPs rs6968704 and rs10486567 were associated with decreased risk of prostate cancer but were not associated with diabetes. All five SNP-prostate cancer relationships did not substantially differ when the analyses were stratified by diabetic status or when diabetic status was controlled for in the model. Furthermore, the association of diabetes with prostate cancer was not altered when the SNPs were included in the logistic model. CONCLUSIONS: These findings indicate that the HNF1B variants are directly associated with both diabetes and prostate cancer, that diabetes does not mediate these gene variant-prostate cancer relationships, and the relationship between these diseases is not mediated through these gene variants. Prostate (c) 2009 Wiley-Liss, Inc
— id: 106469, year: 2009, vol: 70, page: 601, stat: Journal Article,

A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1)
Thomas, Gilles; Jacobs, Kevin B; Kraft, Peter; Yeager, Meredith; Wacholder, Sholom; Cox, David G; Hankinson, Susan E; Hutchinson, Amy; Wang, Zhaoming; Yu, Kai; Chatterjee, Nilanjan; Garcia-Closas, Montserrat; Gonzalez-Bosquet, Jesus; Prokunina-Olsson, Ludmila; Orr, Nick; Willett, Walter C; Colditz, Graham A; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Diver, Ryan; Prentice, Ross; Jackson, Rebecca; Kooperberg, Charles; Chlebowski, Rowan; Lissowska, Jolanta; Peplonska, Beata; Brinton, Louise A; Sigurdson, Alice; Doody, Michele; Bhatti, Parveen; Alexander, Bruce H; Buring, Julie; Lee, I-Min; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Hayes, Richard B; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F Jr; Hoover, Robert N; Chanock, Stephen J; Hunter, David J
2009 May;41(5):579-584, Nature genetics
We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433; P = 6.74 x 10(-10) adjusted genotype test, 2 degrees of freedom) resides in a large linkage disequilibrium block neighboring NOTCH2 and FCGR1B; this signal was stronger for estrogen-receptor-positive tumors. A second SNP on chromosome 14q24.1 (rs999737; P = 1.74 x 10(-7)) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. We also confirmed associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26 and 16q12.1
— id: 139011, year: 2009, vol: 41, page: 579, stat: Journal Article,

CYP19A1 genetic variation in relation to prostate cancer risk and circulating sex hormone concentrations in men from the Breast and Prostate Cancer Cohort Consortium
Travis, Ruth C; Schumacher, Fredrick; Hirschhorn, Joel N; Kraft, Peter; Allen, Naomi E; Albanes, Demetrius; Berglund, Goran; Berndt, Sonja I; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Calle, Eugenia E; Chanock, Stephen; Dunning, Alison M; Hayes, Richard; Feigelson, Heather Spencer; Gaziano, J Michael; Giovannucci, Edward; Haiman, Christopher A; Henderson, Brian E; Kaaks, Rudolf; Kolonel, Laurence N; Ma, Jing; Rodriguez, Laudina; Riboli, Elio; Stampfer, Meir; Stram, Daniel O; Thun, Michael J; Tjonneland, Anne; Trichopoulos, Dimitrios; Vineis, Paolo; Virtamo, Jarmo; Le Marchand, Loic; Hunter, David J
2009 Oct;18(10):2734-2744, Cancer epidemiology biomarkers & prevention
Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNP) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 x 10(-5)], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer
— id: 133724, year: 2009, vol: 18, page: 2734, stat: Journal Article,

Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study
Tsai, Huei-Ting; Caporaso, Neil E; Kyle, Robert A; Katzmann, Jerry A; Dispenzieri, Angela; Hayes, Richard B; Marti, Gerald E; Albitar, Maher; Ghia, Paolo; Rajkumar, S Vincent; Landgren, Ola
2009 Dec 3;114(24):4928-4932, Blood
Immune-related deficiencies are well-known complications of chronic lymphocytic leukemia (CLL). Although recent data indicate that almost all CLL patients are preceded by a monoclonal B-cell lymphocytosis precursor state, patterns of immune defects preceding CLL diagnosis are unclear. We identified 109 persons who developed CLL from the prospective and nationwide Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with 77 469 participants, with serially collected prediagnostic serum samples. We assayed monoclonal (M)-proteins, kappa/lambda free light chains (FLCs) in prediagnostic obtained up to 9.8 years before CLL diagnosis. The prevalence of an abnormal FLC ratio, M-protein, and hypogamma-globulinemia before CLL diagnosis was 38% (95% confidence interval, 29%-47%), 13% (7%-21%), and 3% (1%-8%), respectively. M-proteins and abnormal FLC ratios were detected up to 9.8 years before CLL diagnosis in a total of 48 persons (44%). Hypogammaglobulinemia was not present until 3 years before the diagnosis of CLL. Among 37 patients with information on tumor cell immunophenotype, an association between immunophenotype and involved FLC (P = .024, Fisher exact test) was observed. Among 61 persons with a normal FLC ratio and without an M-protein, 17 had elevated kappa and/or lambda FLC levels, indicating polyclonal B-cell activation in 17 of 109 (16%) patients. These findings support a role for chronic immune stimulation in CLL genesis
— id: 139017, year: 2009, vol: 114, page: 4928, stat: Journal Article,

High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays
Wang, Jun; Lin, Min; Crenshaw, Andrew; Hutchinson, Amy; Hicks, Belynda; Yeager, Meredith; Berndt, Sonja; Huang, Wen-Yi; Hayes, Richard B; Chanock, Stephen J; Jones, Robert C; Ramakrishnan, Ramesh
2009 ;10:561-561, BMC genomics
BACKGROUND: Single nucleotide polymorphisms (SNPs) have emerged as the genetic marker of choice for mapping disease loci and candidate gene association studies, because of their high density and relatively even distribution in the human genomes. There is a need for systems allowing medium multiplexing (ten to hundreds of SNPs) with high throughput, which can efficiently and cost-effectively generate genotypes for a very large sample set (thousands of individuals). Methods that are flexible, fast, accurate and cost-effective are urgently needed. This is also important for those who work on high throughput genotyping in non-model systems where off-the-shelf assays are not available and a flexible platform is needed. RESULTS: We demonstrate the use of a nanofluidic Integrated Fluidic Circuit (IFC) - based genotyping system for medium-throughput multiplexing known as the Dynamic Array, by genotyping 994 individual human DNA samples on 47 different SNP assays, using nanoliter volumes of reagents. Call rates of greater than 99.5% and call accuracies of greater than 99.8% were achieved from our study, which demonstrates that this is a formidable genotyping platform. The experimental set up is very simple, with a time-to-result for each sample of about 3 hours. CONCLUSION: Our results demonstrate that the Dynamic Array is an excellent genotyping system for medium-throughput multiplexing (30-300 SNPs), which is simple to use and combines rapid throughput with excellent call rates, high concordance and low cost. The exceptional call rates and call accuracy obtained may be of particular interest to those working on validation and replication of genome- wide- association (GWA) studies
— id: 139019, year: 2009, vol: 10, page: 561, stat: Journal Article,

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
Willer, Cristen J; Speliotes, Elizabeth K; Loos, Ruth J F; Li, Shengxu; Lindgren, Cecilia M; Heid, Iris M; Berndt, Sonja I; Elliott, Amanda L; Jackson, Anne U; Lamina, Claudia; Lettre, Guillaume; Lim, Noha; Lyon, Helen N; McCarroll, Steven A; Papadakis, Konstantinos; Qi, Lu; Randall, Joshua C; Roccasecca, Rosa Maria; Sanna, Serena; Scheet, Paul; Weedon, Michael N; Wheeler, Eleanor; Zhao, Jing Hua; Jacobs, Leonie C; Prokopenko, Inga; Soranzo, Nicole; Tanaka, Toshiko; Timpson, Nicholas J; Almgren, Peter; Bennett, Amanda; Bergman, Richard N; Bingham, Sheila A; Bonnycastle, Lori L; Brown, Morris; Burtt, Noel P; Chines, Peter; Coin, Lachlan; Collins, Francis S; Connell, John M; Cooper, Cyrus; Smith, George Davey; Dennison, Elaine M; Deodhar, Parimal; Elliott, Paul; Erdos, Michael R; Estrada, Karol; Evans, David M; Gianniny, Lauren; Gieger, Christian; Gillson, Christopher J; Guiducci, Candace; Hackett, Rachel; Hadley, David; Hall, Alistair S; Havulinna, Aki S; Hebebrand, Johannes; Hofman, Albert; Isomaa, Bo; Jacobs, Kevin B; Johnson, Toby; Jousilahti, Pekka; Jovanovic, Zorica; Khaw, Kay-Tee; Kraft, Peter; Kuokkanen, Mikko; Kuusisto, Johanna; Laitinen, Jaana; Lakatta, Edward G; Luan, Jian'an; Luben, Robert N; Mangino, Massimo; McArdle, Wendy L; Meitinger, Thomas; Mulas, Antonella; Munroe, Patricia B; Narisu, Narisu; Ness, Andrew R; Northstone, Kate; O'Rahilly, Stephen; Purmann, Carolin; Rees, Matthew G; Ridderstrale, Martin; Ring, Susan M; Rivadeneira, Fernando; Ruokonen, Aimo; Sandhu, Manjinder S; Saramies, Jouko; Scott, Laura J; Scuteri, Angelo; Silander, Kaisa; Sims, Matthew A; Song, Kijoung; Stephens, Jonathan; Stevens, Suzanne; Stringham, Heather M; Tung, Y C Loraine; Valle, Timo T; Van Duijn, Cornelia M; Vimaleswaran, Karani S; Vollenweider, Peter; Waeber, Gerard; Wallace, Chris; Watanabe, Richard M; Waterworth, Dawn M; Watkins, Nicholas; Witteman, Jacqueline C M; Zeggini, Eleftheria; Zhai, Guangju; Zillikens, M Carola; Altshuler, David; Caulfield, Mark J; Chanock, Stephen J; Farooqi, I Sadaf; Ferrucci, Luigi; Guralnik, Jack M; Hattersley, Andrew T; Hu, Frank B; Jarvelin, Marjo-Riitta; Laakso, Markku; Mooser, Vincent; Ong, Ken K; Ouwehand, Willem H; Salomaa, Veikko; Samani, Nilesh J; Spector, Timothy D; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, Andre G; Wareham, Nicholas J; Deloukas, Panagiotis; Frayling, Timothy M; Groop, Leif C; Hayes, Richard B; Hunter, David J; Mohlke, Karen L; Peltonen, Leena; Schlessinger, David; Strachan, David P; Wichmann, H-Erich; McCarthy, Mark I; Boehnke, Michael; Barroso, Ines; Abecasis, Goncalo R; Hirschhorn, Joel N
2009 Jan;41(1):25-34, Nature genetics
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity
— id: 91731, year: 2009, vol: 41, page: 25, stat: Journal Article,

Estimation of absolute risk for prostate cancer using genetic markers and family history
Xu, Jianfeng; Sun, Jielin; Kader, A Karim; Lindstrom, Sara; Wiklund, Fredrik; Hsu, Fang-Chi; Johansson, Jan-Erik; Zheng, S Lilly; Thomas, Gilles; Hayes, Richard B; Kraft, Peter; Hunter, David J; Chanock, Stephen J; Isaacs, William B; Gronberg, Henrik
2009 Oct 1;69(14):1565-1572, Prostate
BACKGROUND: Multiple DNA sequence variants in the form of single-nucleotide polymorphisms (SNPs) have been found to be reproducibly associated with prostate cancer (PCa) risk. METHODS: Absolute risk for PCa among men with various numbers of inherited risk alleles and family history of PCa was estimated in a population-based case-control study in Sweden (2,893 cases and 1,781 controls), and a nested case-control study from the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening Trial in the U.S. (1,172 cases and 1,157 controls). RESULTS: Increased number of risk alleles and positive family history were independently associated with PCa risk. Considering men with 11 risk alleles (mode) and negative family history as having baseline risk, men who had >or=14 risk alleles and positive family history had an odds ratio (OR) of 4.92 [95% confidence interval (CI): 3.64-6.64] in the Swedish study. These associations were confirmed in the U.S. population. Once a man's SNP genotypes and family history are known, his absolute risk for PCa can be readily calculated and easily interpreted. For example, 55-year-old men with a family history and >or=14 risk alleles have a 52% and 41% risk of being diagnosed with PCa in the next 20 years in the Swedish and U.S. populations, respectively. In comparison, without knowledge of genotype and family history, these men had an average population absolute risk of 13%. CONCLUSION: This risk prediction model may be used to identify men at considerably elevated PCa risk who may be selected for chemoprevention
— id: 139013, year: 2009, vol: 69, page: 1565, stat: Journal Article,

Identification of a new prostate cancer susceptibility locus on chromosome 8q24
Yeager, Meredith; Chatterjee, Nilanjan; Ciampa, Julia; Jacobs, Kevin B; Gonzalez-Bosquet, Jesus; Hayes, Richard B; Kraft, Peter; Wacholder, Sholom; Orr, Nick; Berndt, Sonja; Yu, Kai; Hutchinson, Amy; Wang, Zhaoming; Amundadottir, Laufey; Feigelson, Heather Spencer; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Haiman, Christopher A; Henderson, Brian; Kolonel, Laurence; Le Marchand, Loic; Siddiq, Afshan; Riboli, Elio; Key, Timothy J; Kaaks, Rudolf; Isaacs, William; Isaacs, Sarah; Wiley, Kathleen E; Gronberg, Henrik; Wiklund, Fredrik; Stattin, Par; Xu, Jianfeng; Zheng, S Lilly; Sun, Jielin; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Tucker, Margaret; Gerhard, Daniela S; Hoover, Robert N; Fraumeni, Joseph F Jr; Hunter, David J; Thomas, Gilles; Chanock, Stephen J
2009 Oct;41(10):1055-1057, Nature genetics
We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. We identify a new association with prostate cancer risk on chromosome 8q24 (rs620861, P = 1.3 x 10(-10), heterozygote OR = 1.17, 95% CI 1.10-1.24; homozygote OR = 1.33, 95% CI 1.21-1.45). This defines a new locus associated with prostate cancer susceptibility on 8q24
— id: 139016, year: 2009, vol: 41, page: 1055, stat: Journal Article,

Comprehensive resequence analysis of a 97 kb region of chromosome 10q11.2 containing the MSMB gene associated with prostate cancer
Yeager, Meredith; Deng, Zuoming; Boland, Joseph; Matthews, Casey; Bacior, Jennifer; Lonsberry, Victor; Hutchinson, Amy; Burdett, Laura A; Qi, Liqun; Jacobs, Kevin B; Gonzalez-Bosquet, Jesus; Berndt, Sonja I; Hayes, Richard B; Hoover, Robert N; Thomas, Gilles; Hunter, David J; Dean, Michael; Chanock, Stephen J
2009 Dec;126(6):743-750, Human genetics
Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 10q11.2, harboring the microseminoprotein-beta (MSMB) gene. Both the gene product of MSMB, the prostate secretory protein 94 (PSP94) and its binding protein (PSPBP), have been previously investigated as serum biomarkers for prostate cancer progression. Recent functional work has shown that different alleles of the significantly associated SNP in the promoter of MSMB found to be associated with prostate cancer risk, rs10993994, can influence its expression in tumors and in vitro studies. Since it is plausible that additional variants in this region contribute to the risk of prostate cancer, we have used next-generation sequencing technology to resequence a ~97-kb region that includes the area surrounding MSMB (chr10: 51,168,025-51,265,101) in 36 prostate cancer cases, 26 controls of European origin, and 8 unrelated CEPH individuals in order to identify additional variants to investigate in functional studies. We identified 241 novel polymorphisms within this region, including 142 in the 51-kb block of linkage disequilibrium (LD) that contains rs10993994 and the proximal promoter of MSMB. No sites were observed to be polymorphic within the exons of MSMB
— id: 139014, year: 2009, vol: 126, page: 743, stat: Journal Article,

Variation in KLK genes, prostate-specific antigen and risk of prostate cancer
Ahn, Jiyoung; Berndt, Sonja I; Wacholder, Sholom; Kraft, Peter; Kibel, Adam S; Yeager, Meredith; Albanes, Demetrius; Giovannucci, Edward; Stampfer, Meir J; Virtamo, Jarmo; Thun, Michael J; Feigelson, Heather Spencer; Cancel-Tassin, Geraldine; Cussenot, Olivier; Thomas, Gilles; Hunter, David J; Fraumeni, Joseph F Jr; Hoover, Robert N; Chanock, Stephen J; Hayes, Richard B
2008 Sep;40(9):1032-1034, Nature genetics
— id: 91732, year: 2008, vol: 40, page: 1032, stat: Journal Article,

Serum vitamin D concentration and prostate cancer risk: a nested case-control study
Ahn, Jiyoung; Peters, Ulrike; Albanes, Demetrius; Purdue, Mark P; Abnet, Christian C; Chatterjee, Nilanjan; Horst, Ronald L; Hollis, Bruce W; Huang, Wen-Yi; Shikany, James M; Hayes, Richard B
2008 Jun 4;100(11):796-804, Journal of the National Cancer Institute
BACKGROUND: Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk, and few studies have evaluated whether the associations vary by disease aggressiveness. We investigated the association between vitamin D status, as determined by serum 25-hydroxyvitamin D [25(OH)D] level, and risk of prostate cancer in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. METHODS: The study included 749 case patients with incident prostate cancer who were diagnosed 1-8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry, time since initial screening, and calendar year of cohort entry. All study participants were selected from the trial screening arm (which includes annual standardized prostate cancer screening). Conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) by quintile of season-standardized serum 25(OH)D concentration. Statistical tests were two-sided. RESULTS: No statistically significant trend in overall prostate cancer risk was observed with increasing season-standardized serum 25(OH)D level. However, serum 25(OH)D concentrations greater than the lowest quintile (Q1) were associated with increased risk of aggressive (Gleason sum > or = 7 or clinical stage III or IV) disease (in a model adjusting for matching factors, study center, and history of diabetes, ORs for Q2 vs Q1 = 1.20, 95% CI = 0.80 to 1.81, for Q3 vs Q1 =1.96, 95% CI = 1.34 to 2.87, for Q4 vs Q1 = 1.61, 95% CI = 1.09 to 2.38, and for Q5 vs Q1 = 1.37, 95% CI = 0.92 to 2.05; P(trend) = .05). The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406, 479, 780, 633, and 544 per 100 000 person-years. In exploratory analyses, these associations with aggressive disease were consistent across subgroups defined by age, family history of prostate cancer, diabetes, body mass index, vigorous physical activity, calcium intake, study center, season of blood collection, and assay batch. CONCLUSION: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease
— id: 91708, year: 2008, vol: 100, page: 796, stat: Journal Article,

Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk
Berndt, Sonja I; Potter, John D; Hazra, Aditi; Yeager, Meredith; Thomas, Gilles; Makar, Karen W; Welch, Robert; Cross, Amanda J; Huang, Wen-Yi; Schoen, Robert E; Giovannucci, Edward; Chan, Andrew T; Chanock, Stephen J; Peters, Ulrike; Hunter, David J; Hayes, Richard B
2008 Sep 1;17(17):2665-2672, Human molecular genetics
Several different genetic variants at chromosome 8q24 have been related to prostate, breast and colorectal cancer risk with evidence of region-specific risk differentials for various tumor types. We investigated the association between 15 polymorphisms located in 8q24 regions associated with cancer risk in a pooled analysis of 2587 colorectal adenoma cases, 547 colorectal cancer cases and 2798 controls of European descent from four studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations. Three polymorphisms (rs10808555, rs6983267 and rs7837328) located between 128.47 and 128.54 Mb were found to be associated with colorectal tumor risk. The association was strongest for the previously reported rs6983267 variant and was similar for both adenoma (OR(per allele) = 1.16, 95% CI: 1.07-1.25, P = 0.0002) and cancer (OR (per allele) = 1.17, 95% CI: 1.01-1.35, P = 0.03). The strength of the association of the regional haplotype containing variant alleles at rs10808555, rs6983267 and rs7837328 but not rs10505476 was greater than that of any single variant of both adenoma (OR = 1.27, P = 0.0001) and cancer (OR = 1.26, P = 0.03). The risk associated with rs6983267 was stronger for multiple adenomas (OR(per allele) = 1.29, P = 5.6 x 10(-6)) than for single adenoma (OR(per allele) = 1.10, P = 0.03) with P(heterogeneity) = 0.008. This study confirms the association between colorectal neoplasia and the 8q24 polymorphisms located between 128.47 and 128.54 Mb and suggests a role for these variants in the formation of multiple adenomas
— id: 91710, year: 2008, vol: 17, page: 2665, stat: Journal Article,

Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies
Danforth, Kim N; Hayes, Richard B; Rodriguez, Carmen; Yu, Kai; Sakoda, Lori C; Huang, Wen-Yi; Chen, Bingshu E; Chen, Jinbo; Andriole, Gerald L; Calle, Eugenia E; Jacobs, Eric J; Chu, Lisa W; Figueroa, Jonine D; Yeager, Meredith; Platz, Elizabeth A; Michaud, Dominique S; Chanock, Stephen J; Thun, Michael J; Hsing, Ann W
2008 Mar;29(3):568-572, Carcinogenesis
Chronic inflammation has been hypothesized to increase prostate cancer risk. Prostaglandin-endoperoxide synthase 2 (PTGS2) encodes the proinflammatory cyclooxygenase 2 enzyme believed to be the rate-limiting step in the synthesis of prostaglandins, important mediators of inflammation. We investigated associations between PTGS2 polymorphisms and prostate cancer risk among 2321 prostate cancer cases and 2560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Cancer Prevention Study II Nutrition Cohort. Five single nucleotide polymorphisms (SNPs) (rs5277, rs20432, rs4648276, rs5275 and rs689470) were examined in SNP and haplotype analyses (five SNPs in PLCO and four SNPs in the Nutrition Cohort). In PLCO, the Ex10 +837 T>C marker (rs5275) was initially associated with prostate cancer risk (P-trend = 0.02) but became non-significant after adjustment for multiple comparisons (P = 0.08); this SNP showed no association with prostate cancer risk in the Nutrition Cohort (P-trend = 0.54) or in an analysis pooling the two cohorts (P-trend = 0.20). No other SNP was associated with prostate cancer risk in PLCO or the Nutrition Cohort individually or combined. Haplotype analyses suggested an association between PTGS2 variants in PLCO alone (global P = 0.007), but not in the Nutrition Cohort (global P = 0.78) or pooled analysis (global P = 0.18). In conclusion, despite the potential importance of inflammation in prostate carcinogenesis, results from our large study of five PTGS2 SNPs does not support a strong association between PTGS2 variants and prostate cancer risk in non-Hispanic white men
— id: 91689, year: 2008, vol: 29, page: 568, stat: Journal Article,

TNF polymorphisms and prostate cancer risk
Danforth, Kim N; Rodriguez, Carmen; Hayes, Richard B; Sakoda, Lori C; Huang, Wen-Yi; Yu, Kai; Calle, Eugenia E; Jacobs, Eric J; Chen, Bingshu E; Andriole, Gerald L; Figueroa, Jonine D; Yeager, Meredith; Platz, Elizabeth A; Michaud, Dominique S; Chanock, Stephen J; Thun, Michael J; Hsing, Ann W
2008 Mar 1;68(4):400-407, Prostate
BACKGROUND: Inflammation has been hypothesized to increase prostate cancer risk. Tumor necrosis factor (TNF) is an important mediator of the inflammatory process, but the relationship between TNF variants and prostate cancer remains unclear. METHODS: We examined associations between six TNF single nucleotide polymorphisms (SNPs) (rs1799964, rs1800630, rs1799724, rs1800629, rs361525, rs1800610) and prostate cancer risk among 2,321 cases and 2,560 controls from two nested case-control studies within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 2,561, 5 SNPs) and the Cancer Prevention Study II Nutrition Cohort (Nutrition Cohort, n = 2,320, 6 SNPs). Odds ratios and 95% confidence intervals were estimated for individual SNPs and haplotypes in each cohort separately and in pooled analyses. RESULTS: No TNF SNP was associated with prostate cancer risk in PLCO (P-trend > or = 0.16), while in the Nutrition Cohort, associations were significant for 2 highly correlated variants (rs1799724, 1800610, r2 = 0.95; P-trend = 0.04 and 0.02, respectively). In pooled analyses, no single SNP was associated with prostate cancer risk (P-trend > or = 0.08). After adjustment for multiple testing, no SNP was associated with prostate cancer risk in either cohort individually or in the pooled analysis (P-trend all > or = 0.10). Haplotypes based on 5 TNF SNPs did not vary by case/control status in PLCO, but showed marginal associations in the Nutrition Cohort (global P = 0.06) and the pooled analysis (global P = 0.05). CONCLUSIONS: Despite somewhat suggestive haplotype results, overall our study does not support an association between TNF variants and prostate cancer risk
— id: 91698, year: 2008, vol: 68, page: 400, stat: Journal Article,

Genetic variation in sodium-dependent vitamin C transporters SLC23A1 and SLC23A2 and risk of advanced colorectal adenoma
Erichsen, Hans Christian; Peters, Ulrike; Eck, Peter; Welch, Robert; Schoen, Robert E; Yeager, Meredith; Levine, Mark; Hayes, Richard B; Chanock, Stephen
2008 ;60(5):652-659, Nutrition & cancer
Previous observational studies suggest that vitamin C may reduce risk of colorectal cancer. Vitamin C transport is facilitated by membrane bound sodium-dependent transporters, SVCT1 (encoded by SLC23A1) and SVCT2 (encoded by SLC23A2). To investigate if common genetic variants in these two genes are associated with risk of colorectal tumor development, we conducted a case-control study of 656 Caucasian advanced distal colorectal adenoma cases and 665 Caucasian sigmoidoscopy-negative controls nested within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The analysis of common single nucleotide polymorphisms in SLC23A1 revealed no association. For SLC23A2, overall, there was no association with haplotypes, but two SNPs located in intron 8 and exon 11 could be associated (odds ratio = 0.49, 95% confidence interval = 0.25-0.95 for haplotype G-C vs. haplotype C-C). The findings should be confirmed in follow-up studies, and further investigation is required to probe the functional basis of this finding
— id: 91721, year: 2008, vol: 60, page: 652, stat: Journal Article,

Involuntary smoking and head and neck cancer risk: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium
Lee, Yuan-Chin Amy; Boffetta, Paolo; Sturgis, Erich M; Wei, Qingyi; Zhang, Zuo-Feng; Muscat, Joshua; Lazarus, Philip; Matos, Elena; Hayes, Richard B; Winn, Deborah M; Zaridze, David; Wunsch-Filho, Victor; Eluf-Neto, Jose; Koifman, Sergio; Mates, Dana; Curado, Maria Paula; Menezes, Ana; Fernandez, Leticia; Daudt, Alexander W; Szeszenia-Dabrowska, Neonila; Fabianova, Eleonora; Rudnai, Peter; Ferro, Gilles; Berthiller, Julien; Brennan, Paul; Hashibe, Mia
2008 Aug;17(8):1974-1981, Cancer epidemiology biomarkers & prevention
Although active tobacco smoking has been identified as a major risk factor for head and neck cancer, involuntary smoking has not been adequately evaluated because of the relatively low statistical power in previous studies. We took advantage of data pooled in the International Head and Neck Cancer Epidemiology Consortium to evaluate the role of involuntary smoking in head and neck carcinogenesis. Involuntary smoking exposure data were pooled across six case-control studies in Central Europe, Latin America, and the United States. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542 cases and 2,197 controls who reported never using tobacco, and the heterogeneity among the study-specific ORs was assessed. In addition, stratified analyses were done by subsite. No effect of ever involuntary smoking exposure either at home or at work was observed for head and neck cancer overall. However, long duration of involuntary smoking exposure at home and at work was associated with an increased risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; P(trend) < 0.01; OR for >15 years at work, 1.55; 95% CI, 1.04-2.30; P(trend) = 0.13). The effect of duration of involuntary smoking exposure at home was stronger for pharyngeal and laryngeal cancers than for other subsites. An association between involuntary smoking exposure and the risk of head and neck cancer, particularly pharyngeal and laryngeal cancers, was observed for long duration of exposure. These results are consistent with those for active smoking and suggest that elimination of involuntary smoking exposure might reduce head and neck cancer risk among never smokers
— id: 91717, year: 2008, vol: 17, page: 1974, stat: Journal Article,

Identification of ten loci associated with height highlights new biological pathways in human growth
Lettre, Guillaume; Jackson, Anne U; Gieger, Christian; Schumacher, Fredrick R; Berndt, Sonja I; Sanna, Serena; Eyheramendy, Susana; Voight, Benjamin F; Butler, Johannah L; Guiducci, Candace; Illig, Thomas; Hackett, Rachel; Heid, Iris M; Jacobs, Kevin B; Lyssenko, Valeriya; Uda, Manuela; Boehnke, Michael; Chanock, Stephen J; Groop, Leif C; Hu, Frank B; Isomaa, Bo; Kraft, Peter; Peltonen, Leena; Salomaa, Veikko; Schlessinger, David; Hunter, David J; Hayes, Richard B; Abecasis, Goncalo R; Wichmann, H-Erich; Mohlke, Karen L; Hirschhorn, Joel N
2008 May;40(5):584-591, Nature genetics
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait
— id: 91704, year: 2008, vol: 40, page: 584, stat: Journal Article,

Common variants near MC4R are associated with fat mass, weight and risk of obesity
Loos, Ruth J F; Lindgren, Cecilia M; Li, Shengxu; Wheeler, Eleanor; Zhao, Jing Hua; Prokopenko, Inga; Inouye, Michael; Freathy, Rachel M; Attwood, Antony P; Beckmann, Jacques S; Berndt, Sonja I; Jacobs, Kevin B; Chanock, Stephen J; Hayes, Richard B; Bergmann, Sven; Bennett, Amanda J; Bingham, Sheila A; Bochud, Murielle; Brown, Morris; Cauchi, Stephane; Connell, John M; Cooper, Cyrus; Smith, George Davey; Day, Ian; Dina, Christian; De, Subhajyoti; Dermitzakis, Emmanouil T; Doney, Alex S F; Elliott, Katherine S; Elliott, Paul; Evans, David M; Sadaf Farooqi, I; Froguel, Philippe; Ghori, Jilur; Groves, Christopher J; Gwilliam, Rhian; Hadley, David; Hall, Alistair S; Hattersley, Andrew T; Hebebrand, Johannes; Heid, Iris M; Lamina, Claudia; Gieger, Christian; Illig, Thomas; Meitinger, Thomas; Wichmann, H-Erich; Herrera, Blanca; Hinney, Anke; Hunt, Sarah E; Jarvelin, Marjo-Riitta; Johnson, Toby; Jolley, Jennifer D M; Karpe, Fredrik; Keniry, Andrew; Khaw, Kay-Tee; Luben, Robert N; Mangino, Massimo; Marchini, Jonathan; McArdle, Wendy L; McGinnis, Ralph; Meyre, David; Munroe, Patricia B; Morris, Andrew D; Ness, Andrew R; Neville, Matthew J; Nica, Alexandra C; Ong, Ken K; O'Rahilly, Stephen; Owen, Katharine R; Palmer, Colin N A; Papadakis, Konstantinos; Potter, Simon; Pouta, Anneli; Qi, Lu; Randall, Joshua C; Rayner, Nigel W; Ring, Susan M; Sandhu, Manjinder S; Scherag, Andre; Sims, Matthew A; Song, Kijoung; Soranzo, Nicole; Speliotes, Elizabeth K; Syddall, Holly E; Teichmann, Sarah A; Timpson, Nicholas J; Tobias, Jonathan H; Uda, Manuela; Vogel, Carla I Ganz; Wallace, Chris; Waterworth, Dawn M; Weedon, Michael N; Willer, Cristen J; Yuan, Xin; Zeggini, Eleftheria; Hirschhorn, Joel N; Strachan, David P; Ouwehand, Willem H; Caulfield, Mark J; Samani, Nilesh J; Frayling, Timothy M; Vollenweider, Peter; Waeber, Gerard; Mooser, Vincent; Deloukas, Panos; McCarthy, Mark I; Wareham, Nicholas J; Barroso, Ines; Jacobs, Kevin B; Chanock, Stephen J; Hayes, Richard B; Lamina, Claudia; Gieger, Christian; Illig, Thomas; Meitinger, Thomas; Wichmann, H-Erich; Kraft, Peter; Hankinson, Susan E; Hunter, David J; Hu, Frank B; Lyon, Helen N; Voight, Benjamin F; Ridderstrale, Martin; Groop, Leif; Scheet, Paul; Sanna, Serena; Abecasis, Goncalo R; Albai, Giuseppe; Nagaraja, Ramaiah; Schlessinger, David; Jackson, Anne U; Tuomilehto, Jaakko; Collins, Francis S; Boehnke, Michael; Mohlke, Karen L
2008 Jun;40(6):768-775, Nature genetics
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits
— id: 91705, year: 2008, vol: 40, page: 768, stat: Journal Article,

Variation in the selenoenzyme genes and risk of advanced distal colorectal adenoma
Peters, Ulrike; Chatterjee, Nilanjan; Hayes, Richard B; Schoen, Robert E; Wang, Yinghui; Chanock, Stephen J; Foster, Charles B
2008 May;17(5):1144-1154, Cancer epidemiology biomarkers & prevention
BACKGROUND: Epidemiologic and animal studies provide evidence for a chemopreventive effect of selenium on colorectal cancer, which may be mediated by the antioxidative and anti-inflammatory properties of selenoenzymes. We therefore investigated whether genetic variants in selenoenzymes abundantly expressed in the colon are associated with advanced colorectal adenoma, a cancer precursor. METHODS: Cases with a left-sided advanced adenoma (n = 772) and matched controls (n = 777) screen negative for polyps based on sigmoidoscopy examination were randomly selected from participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The underlying genetic variation was determined by resequencing. We genotyped 44 tagging single nucleotide polymorphisms (SNP) in six genes [glutathione peroxidase 1-4 (GPX1, GPX2, GPX3, and GPX4), selenoprotein P (SEPP1), and thioredoxin reductase 1 (TXNRD1)] to efficiently predict common variation across these genes. RESULTS: Four variants in SEPP1 were significantly associated with advanced adenoma risk. A rare variant in the 5' region of SEPP1 (-4166C>G) was present in nine cases but in none of the controls (exact P = 0.002). Three SNPs located in the 3' region of SEPP1, which is overlapping with the promoter region of an antisense transcript, were significantly associated with adenoma risk: homozygotes at two SEPP1 loci (31,174 bp 3' of STP A>G and 43,881 bp 3' of STP G>A) were associated with increased adenoma risk [odds ratio (OR), 1.48; 95% confidence interval (95% CI), 1.00-2.19 and OR, 1.53; 95% CI, 1.05-2.22, respectively] and the variant SEPP1 44,321 bp 3' of STP C>T was associated with a reduced adenoma risk (CT versus CC OR, 0.85; 95% CI, 0.63-1.15). Furthermore, we observed a significant 80% reduction for advanced colorectal adenoma risk for carriers of the variant allele at TXNRD1 IVS1-181C>G (OR, 0.20; 95% CI, 0.07-0.55; P trend = 0.004). Consistent with the individual SNP results, we observed a significant overall association with adenoma risk for SEPP1 and TXNRD1 (global P = 0.02 and 0.008, respectively) but not for the four GPX genes. CONCLUSION: Our study suggests that genetic variants at or near the SEPP1 and TXNRD1 loci may be associated with advanced colorectal adenoma. As this is the first study to comprehensively investigate this hypothesis, confirmation in independent study populations is needed
— id: 91706, year: 2008, vol: 17, page: 1144, stat: Journal Article,

Multiple loci identified in a genome-wide association study of prostate cancer
Thomas, Gilles; Jacobs, Kevin B; Yeager, Meredith; Kraft, Peter; Wacholder, Sholom; Orr, Nick; Yu, Kai; Chatterjee, Nilanjan; Welch, Robert; Hutchinson, Amy; Crenshaw, Andrew; Cancel-Tassin, Geraldine; Staats, Brian J; Wang, Zhaoming; Gonzalez-Bosquet, Jesus; Fang, Jun; Deng, Xiang; Berndt, Sonja I; Calle, Eugenia E; Feigelson, Heather Spencer; Thun, Michael J; Rodriguez, Carmen; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Giovannucci, Edward; Willett, Walter C; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F Jr; Hoover, Robert; Hayes, Richard B; Hunter, David J; Chanock, Stephen J
2008 Mar;40(3):310-315, Nature genetics
We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals
— id: 91699, year: 2008, vol: 40, page: 310, stat: Journal Article,

Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review
Varela-Lema, Leonor; Taioli, Emanuela; Ruano-Ravina, Alberto; Barros-Dios, Juan M; Anantharaman, Devasena; Benhamou, Simone; Boccia, Stefania; Bhisey, Rajani A; Cadoni, Gabriella; Capoluongo, Ettore; Chen, Chien-Jen; Foulkes, William; Goloni-Bertollo, Eny Maria; Hatagima, Ana; Hayes, Richard B; Katoh, Takahiko; Koifman, Sergio; Lazarus, Phillip; Manni, Johannes J; Mahimkar, Manoj; Morita, Shunji; Park, Jong; Park, Kwang-Kyun; Pavarino Bertelli, Erika Cristina; de Souza Fonseca Ribeiro, Enilze Maria; Roy, Bidyut; Spitz, Margaret R; Strange, Richard C; Wei, Qingyi; Ragin, Camille C
2008 Jun;10(6):369-384, Genetics in medicine
The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html ). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9-3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9-1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4-2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3-3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1-1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer
— id: 91707, year: 2008, vol: 10, page: 369, stat: Journal Article,

Endogenous sex hormones and the risk of prostate cancer: a prospective study
Weiss, Jocelyn M; Huang, Wen-Yi; Rinaldi, Sabina; Fears, Thomas R; Chatterjee, Nilanjan; Hsing, Ann W; Crawford, E David; Andriole, Gerald L; Kaaks, Rudolf; Hayes, Richard B
2008 May 15;122(10):2345-2350, International journal of cancer
Sex steroid hormones influence prostate development and maintenance through their roles in prostate cellular proliferation, differentiation and apoptosis. Although suspected to be involved in prostate carcinogenesis, an association between circulating androgens and prostate cancer has not been clearly established in epidemiologic studies. We conducted a nested case-control study with prospectively collected samples in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, to examine associations of prostate cancer with androstenedione (Delta4-A), testosterone (T), sex hormone-binding globulin (SHBG) and 3alpha-androstanediol glucuronide (3alpha-diolG). A total of 727 incident Caucasian prostate cancer cases (age >/= 65 years, N = 396) and 889 matched controls were selected for this analysis. Overall, prostate cancer risks were unrelated to serum T, estimated free and bioavailable T, and SHBG; however, risks increased with increasing T:SHBG ratio (p(trend) = 0.01), mostly related to risk in older men (>/=65 years, p(trend) = 0.001), particularly for aggressive disease [highest versus lowest quartile: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.50-5.09]. No clear patterns were noted for Delta4-A and 3alpha-diolG. In summary, our large prospective study did not show convincing evidence of a relationship between serum sex hormones and prostate cancer. T:SHBG ratio was related to risk in this older population of men, but the significance of this ratio in steroidal biology is unclear. (c) 2008 Wiley-Liss, Inc
— id: 91697, year: 2008, vol: 122, page: 2345, stat: Journal Article,

Comprehensive resequence analysis of a 136 kb region of human chromosome 8q24 associated with prostate and colon cancers
Yeager, Meredith; Xiao, Nianqing; Hayes, Richard B; Bouffard, Pascal; Desany, Brian; Burdett, Laura; Orr, Nick; Matthews, Casey; Qi, Liqun; Crenshaw, Andrew; Markovic, Zdenek; Fredrikson, Karin M; Jacobs, Kevin B; Amundadottir, Laufey; Jarvie, Thomas P; Hunter, David J; Hoover, Robert; Thomas, Gilles; Harkins, Timothy T; Chanock, Stephen J
2008 Sep;124(2):161-170, Human genetics
Recently, genome-wide association studies have identified loci across a segment of chromosome 8q24 (128,100,000-128,700,000) associated with the risk of breast, colon and prostate cancers. At least three regions of 8q24 have been independently associated with prostate cancer risk; the most centromeric of which appears to be population specific. Haplotypes in two contiguous but independent loci, marked by rs6983267 and rs1447295, have been identified in the Cancer Genetic Markers of Susceptibility project ( http://cgems.cancer.gov ), which genotyped more than 5,000 prostate cancer cases and 5,000 controls of European origin. The rs6983267 locus is also strongly associated with colorectal cancer. To ascertain a comprehensive catalog of common single-nucleotide polymorphisms (SNPs) across the two regions, we conducted a resequence analysis of 136 kb (chr8: 128,473,000-128,609,802) using the Roche/454 next-generation sequencing technology in 39 prostate cancer cases and 40 controls of European origin. We have characterized a comprehensive catalog of common (MAF > 1%) SNPs within this region, including 442 novel SNPs and have determined the pattern of linkage disequilibrium across the region. Our study has generated a detailed map of genetic variation across the region, which should be useful for choosing SNPs for fine mapping of association signals in 8q24 and investigations of the functional consequences of select common variants
— id: 91716, year: 2008, vol: 124, page: 161, stat: Journal Article,

Dairy products, calcium intake, and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial
Ahn, Jiyoung; Albanes, Demetrius; Peters, Ulrike; Schatzkin, Arthur; Lim, Unhee; Freedman, Michal; Chatterjee, Nilanjan; Andriole, Gerald L; Leitzmann, Michael F; Hayes, Richard B
2007 Dec;16(12):2623-2630, Cancer epidemiology biomarkers & prevention
Higher intakes of calcium and dairy products, a major source of dietary calcium, are reported to increase the risk of prostate cancer, potentially due to reductions in circulating vitamin D with increasing calcium intake. We prospectively examined the association of dairy product and calcium intake with prostate cancer risk in 29,509 men, including 1,910 cases, in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We also evaluated the relation of calcium intake with serum 25-hydroxy-vitamin D [25(OH)D] and 1,25-dihydroxy-vitamin D [1,25(OH)(2)D], in a Prostate, Lung, Colorectal, and Ovarian Trial substudy (n = 275). Dietary intake was assessed using a food frequency questionnaire. Baseline serum 1,25(OH)(2)D was determined by RIA. Greater intake of dairy products, particularly low-fat dairy products, was weakly associated with increased risk of prostate cancer [relative risk (RR), 1.12; 95% confidence intervals (CI), 0.97-1.30; P trend = 0.06 for >2.75 versus < or = 0.98 servings of total dairy/day; 1.23 (1.07-1.41) for low-fat dairy]. Greater dietary calcium intake was associated with increased risk of prostate cancer (RR, 1.34; 95% CI, 0.93-1.94; P trend = 0.02 for >2,000 versus <1,000 mg/day), but greater supplementary calcium intake was not associated with the risk. Associations of dairy product and dietary calcium intake were evident for nonaggressive disease (RR, 1.20; 95% CI, 0.99-1.46; P trend = 0.01 for dairy products; 1.64, 1.04-2.57; P trend = 0.002 for dietary calcium), but not aggressive disease (RR, 1.02; 95% CI, 0.81-1.28 for dairy products; 0.94, 0.49-1.80 for dietary calcium). Calcium intake was not associated with serum 25-hydroxy-vitamin D and 1,25(OH)(2)D concentration. In this large prospective study in a prostate cancer screening trial, greater dietary intake of calcium and dairy products, particularly low-fat types, may be modestly associated with increased risks for nonaggressive prostate cancer, but was unrelated to aggressive disease. Furthermore, we found no relationship between calcium intake and circulating vitamin D
— id: 91693, year: 2007, vol: 16, page: 2623, stat: Journal Article,

Variant in sex hormone-binding globulin gene and the risk of prostate cancer
Berndt, Sonja I; Chatterjee, Nilanjan; Huang, Wen-Yi; Chanock, Stephen J; Welch, Robert; Crawford, E David; Hayes, Richard B
2007 Jan;16(1):165-168, Cancer epidemiology biomarkers & prevention
Sex hormones have been implicated in prostate carcinogenesis and are thought to modulate cell proliferation and growth. To investigate the association between polymorphisms in hormone-related genes and prostate cancer risk, we conducted a two-stage, case-control study within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Using DNA extracted from blood specimens, we initially genotyped 14 single nucleotide polymorphisms in genes involved in hormone regulation or metabolism (AKR1C3, CYP1A1, CYP1B1, CYP3A4, ESR1, GNRH1, HSD173B, HSD3B2, SHBG, and SRD5A2) in 488 prostate cancer cases and 617 matched controls. Heterozygotes at SHBG D356N were found to be associated with an increased risk of prostate cancer compared with the homozygous wild type, particularly among non-Hispanic whites (odds ratio, 1.54; 95% confidence interval, 1.13-2.09; P = 0.006). No significant associations were observed with the other polymorphisms. The SHBG D356N polymorphism, which has potential functional significance, was subsequently genotyped in additional 769 cases and 1,168 controls. Overall, SHBG D356N heterozygotes were found to have an increased risk of prostate cancer among whites (odds ratio, 1.34; 95% confidence interval, 1.10-1.63; P = 0.0007). This study suggests that genetic variation in SHBG may influence prostate cancer susceptibility
— id: 91654, year: 2007, vol: 16, page: 165, stat: Journal Article,

Transforming growth factor beta 1 (TGFB1) gene polymorphisms and risk of advanced colorectal adenoma
Berndt, Sonja I; Huang, Wen-Yi; Chatterjee, Nilanjan; Yeager, Meredith; Welch, Robert; Chanock, Stephen J; Weissfeld, Joel L; Schoen, Robert E; Hayes, Richard B
2007 Sep;28(9):1965-1970, Carcinogenesis
Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine that has been implicated in the pathogenesis of colorectal neoplasia. To investigate the association between genetic variants in TGFB1 and the risk of colorectal adenoma, we conducted a case-control study of 754 advanced adenoma cases and 769 controls from the baseline screening exam of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma (>or=1 cm, high-grade dysplasia or villous characteristics), and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy. DNA was extracted from blood specimens, and five single-nucleotide polymorphisms in TGFB1 of known or suggested functional significance (-800G>A, -509C>T, Leu10Pro, Arg25Pro and Thr263Ile) were genotyped. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between each polymorphism and adenoma. The high TGFB1 producer genotypes, -509TT and 10Pro/Pro, were associated with an increased risk of colorectal adenoma compared with other genotypes (OR = 1.51, 95% CI: 1.04-2.20 and OR = 1.37, 95% CI: 1.02-1.86, respectively). These increased risks, particularly for -509TT, were greater for persons with multiple adenomas (OR = 1.89, 95% CI: 1.16-3.09, P = 0.01) and individuals with rectal adenoma (OR = 2.95, 95% CI: 1.66-5.26, P = 0.0002). Haplotype analysis revealed similar findings under a recessive model. No associations were observed for polymorphisms at codons 25 and 263. In conclusion, variants that enhance TGFB1 production may be associated with an increased risk of advanced colorectal adenoma
— id: 91678, year: 2007, vol: 28, page: 1965, stat: Journal Article,

Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma
Berndt, Sonja I; Huang, Wen-Yi; Fallin, M Daniele; Helzlsouer, Kathy J; Platz, Elizabeth A; Weissfeld, Joel L; Church, Timothy R; Welch, Robert; Chanock, Stephen J; Hayes, Richard B
2007 Feb 1;67(3):1395-1404, Cancer research
Base excision repair (BER) corrects DNA damage caused by oxidative stress and low folate intake, which are putative risk factors for colorectal neoplasia. To examine the relationship between genetic variation in BER genes and colorectal adenoma risk, we conducted a case-control study of 767 cases of advanced colorectal adenoma and 773 controls from the baseline screening exam of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma, and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy, frequency-matched to cases on race and gender. Twenty single nucleotide polymorphisms were genotyped in four BER genes (APEX1, PARP1, POLB, and XRCC1), and conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association with colorectal adenoma. Two variants with possible functional significance were associated with risk. The APEX1 51H variant was associated with a borderline significant decreased risk of colorectal adenoma (OR, 0.66; 95% CI, 0.44-1.00), and the XRCC1 399Q variant was inversely associated with risk among Caucasians (OR, 0.80; 95% CI, 0.64-0.99). Homozygotes at two PARP1 loci (A284A and IVS13+118G>A) were also associated with a decreased risk of colorectal adenoma compared with wild-type carriers (OR, 0.70; 95% CI, 0.49-0.98 for both), which was restricted to advanced adenomas displaying histologically aggressive characteristics (OR, 0.51; 95% CI, 0.33-0.78, P = 0.002 for PARP1 A284A). This study suggests that polymorphisms in APEX1, XRCC1, and PARP1 may be associated with advanced colorectal adenoma
— id: 91657, year: 2007, vol: 67, page: 1395, stat: Journal Article,

Reply to the letter to the Editor: "N-Acetyltransferases and the susceptibility to benzidine-induced bladder carcinogenesis"
Carreon, Tania; Kadlubar, Fred F; Ruder, Avima M; Schulte, Paul A; Hayes, Richard B; Waters, Martha; Grant, Delores J; Boissy, Robert; Bell, Douglas A; Hemstreet, George P 3rd; Yin, Songnian; Lemasters, Grace K; Rothman, Nathaniel
2007 Oct 1;121(7):1637-1639, International journal of cancer
— id: 91674, year: 2007, vol: 121, page: 1637, stat: Journal Article,

Sequence variants of estrogen receptor beta and risk of prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Chen, Yen-Ching; Kraft, Peter; Bretsky, Philip; Ketkar, Shamika; Hunter, David J; Albanes, Demetrius; Altshuler, David; Andriole, Gerald; Berg, Christine D; Boeing, Heiner; Burtt, Noel; Bueno-de-Mesquita, Bas; Cann, Howard; Canzian, Federico; Chanock, Stephen; Dunning, Alison; Feigelson, Heather S; Freedman, Matthew; Gaziano, J Michael; Giovannucci, Edward; Sanchez, Maria-Jose; Haiman, Christopher A; Hallmans, Goran; Hayes, Richard B; Henderson, Brian E; Hirschhorn, Joel; Kaaks, Rudolf; Key, Timothy J; Kolonel, Laurence N; LeMarchand, Loic; Ma, Jing; Overvad, Kim; Palli, Domenico; Pharaoh, Paul; Pike, Malcolm; Riboli, Eliot; Rodriguez, Carmen; Setiawan, V Wendy; Stampfer, Meir; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Travis, Ruth C; Virtamo, Jarmo; Trichopoulou, Antonia; Wacholder, Sholom; Weinstein, Stephanie J
2007 Oct;16(10):1973-1981, Cancer epidemiology biomarkers & prevention
BACKGROUND: Estrogen receptor beta (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis. METHODS: We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group. We characterized genetic variation in ESR2 by resequencing exons in 190 breast and prostate cancer cases and genotyping a dense set of single nucleotide polymorphisms (SNP) spanning the locus in a multiethnic panel of 349 cancer-free subjects. We selected four haplotype-tagging SNPs (htSNP) to capture common ESR2 variation in Whites; these htSNPs were then genotyped in all cohorts. Conditional logistic regression models were used to assess the association between sequence variants of ESR2 and the risk of prostate cancer. We also investigated the effect modification by age, body mass index, and family history, as well as the association between sequence variants of ESR2 and advanced-stage (>or=T3b, N1, or M1) and high-grade (Gleason sum >or=8) prostate cancer, respectively. RESULTS: The four tag SNPs in ESR2 were not significantly associated with prostate cancer risk, individually. The global test for the influence of any haplotype on the risk of prostate cancer was not significant (P = 0.31). However, we observed that men carrying two copies of one of the variant haplotypes (TACC) had a 1.46-fold increased risk of prostate cancer (99% confidence interval, 1.06-2.01) compared with men carrying zero copies of this variant haplotype. No SNPs or haplotypes were associated with advanced stage or high grade of prostate cancer. CONCLUSION: In our analysis focused on genetic variation common in Whites, we observed little evidence for any substantial association of inherited variation in ESR2 with risk of prostate cancer. A nominally significant (P < 0.01) association between the TACC haplotype and prostate cancer risk under the recessive model could be a chance finding and, in any event, would seem to contribute only slightly to the overall burden of prostate cancer
— id: 91687, year: 2007, vol: 16, page: 1973, stat: Journal Article,

RNASEL Arg462Gln polymorphism and prostate cancer in PLCO
Daugherty, Sarah E; Hayes, Richard B; Yeager, Meredith; Andriole, Gerald L; Chatterjee, Nilanjan; Huang, Wen-Yi; Isaacs, William B; Platz, Elizabeth A
2007 Jun 1;67(8):849-854, Prostate
BACKGROUND: The Gln allele of the Arg462Gln polymorphism in RNASEL results in a threefold decrease in enzymatic activity, a reported deficiency in apoptotic response, and has been associated with prostate cancer in some high-risk family studies. The relationship of this variant to sporadic prostate cancer remains uncertain. METHODS: We conducted a nested case-control study of 1,317 prostate cancer cases and 1,842 controls from the screening arm of the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. Conditional logistic regression was used to evaluate the association between the RNASEL Arg462Gln polymorphism and prostate cancer. RESULTS: No statistically significant association was observed between the Arg462Gln polymorphism and prostate cancer (compared to Arg/Arg, Gln/Arg: OR= 0.99 95% CI 0.84-1.16; Gln/Gln: OR= 0.95 95% CI 0.74-1.21), although slight non-significant differences in risk were observed among men with the Gln/Gln genotype by stage and grade. CONCLUSIONS: These results suggest that the RNASEL Gln/Gln genotype does not play an important role in the etiology of prostate cancer in the general population
— id: 91661, year: 2007, vol: 67, page: 849, stat: Journal Article,

Variants in the alpha-Methylacyl-CoA racemase gene and the association with advanced distal colorectal adenoma
Daugherty, Sarah E; Platz, Elizabeth A; Shugart, Yin Yao; Fallin, M Daniele; Isaacs, William B; Chatterjee, Nilanjin; Welch, Robert; Huang, Wen-Yi; Hayes, Richard B
2007 Aug;16(8):1536-1542, Cancer epidemiology biomarkers & prevention
BACKGROUND: alpha-Methylacyl-CoA racemase (AMACR), an enzyme involved in oxidation of branched chain fatty acids and cholesterol metabolites, as well as ibuprofen metabolism, is overexpressed in colorectal adenomas and cancer. AMACR gene variants have been associated with hereditary prostate cancer, but no studies have evaluated their etiologic role in colorectal carcinogenesis. METHODS: We conducted a case-control study of 725 advanced distal colorectal adenoma cases and 729 frequency-matched controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Seven AMACR polymorphisms were genotyped. Unconditional logistic regression models were used to evaluate the associations adjusting for age at randomization and gender. RESULTS: The 201L allele of S201L [TT versus CC: odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.15-2.62; TC versus CC: OR, 1.17; 95% CI, 0.93-1.49] and the 277E allele of K277E (GG versus AA: OR, 1.66; 95% CI, 1.03-2.68; GA versus AA: OR, 1.21; 95% CI, 0.96-1.53) were associated with increased risk of advanced distal colorectal adenoma (both P(trend) </= 0.02); the TGTGCG haplotype of six informative single nucleotide polymorphisms was also associated with increased risk (OR, 1.27; 95% CI, 1.03-1.55). Regular ibuprofen users who were homozygous for the variant allele at either M9V or D175G were at reduced risk for adenoma (both P(interaction) < 0.05). CONCLUSION: Our study identified variants in AMACR associated with advanced distal colorectal adenoma and pointed to potential interactions with ibuprofen use
— id: 91683, year: 2007, vol: 16, page: 1536, stat: Journal Article,

Polymorphic variants in alpha-methylacyl-CoA racemase and prostate cancer
Daugherty, Sarah E; Shugart, Yin Yao; Platz, Elizabeth A; Fallin, M Daniele; Isaacs, William B; Pfeiffer, Ruth M; Welch, Robert; Huang, Wen-Yi; Reding, Douglas; Hayes, Richard B
2007 Oct 1;67(14):1487-1497, Prostate
BACKGROUND: Alpha-methylacyl-CoA racemase (AMACR), which prepares branched chain fatty acids to be metabolized for energy and is implicated in the activation of the COX-inhibiting form of ibuprofen, is overexpressed in prostate cancer and its precursor lesions. Significant differences in AMACR allele frequencies have been reported for hereditary prostate cancer (HPC), but the relevance of AMACR in the context of its substrates have not been studied. METHODS: We conducted a nested case-control study of 1,318 prostate cancer cases and 1,842 controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Five non-synonymous (nsSNP) and two intronic AMACR polymorphisms were genotyped. Conditional logistic regression models were used to evaluate the associations between the genetic variants and prostate cancer. RESULTS: Overall, prostate cancer was not related to AMACR gene variants; however, risks for prostate cancer were significantly reduced among regular ibuprofen users who carried allele variants at four nsSNP loci (M9V, D175G, S201L, and K277E; all P(trend) < 0.05) or carried the TGTGCG haplotype (OR = 0.65; 95% CI 0.44-0.97). No AMACR-related associations were noted among nonregular ibuprofen users (all P(interaction) > 0.33). CONCLUSION: AMACR gene variants were unrelated to prostate cancer overall in this study. The protective associations observed among ibuprofen users suggest that AMACR gene variants may enhance the chemopreventive effects of ibuprofen on prostate cancer risk
— id: 91682, year: 2007, vol: 67, page: 1487, stat: Journal Article,

Adherence to the USDA Food Guide, DASH Eating Plan, and Mediterranean dietary pattern reduces risk of colorectal adenoma
Dixon, L Beth; Subar, Amy F; Peters, Ulrike; Weissfeld, Joel L; Bresalier, Robert S; Risch, Adam; Schatzkin, Arthur; Hayes, Richard B
2007 Nov;137(11):2443-2450, Journal of nutrition
The 2005 Dietary Guidelines for Americans include quantitative recommendations for 2 eating patterns, the USDA Food Guide and the Dietary Approaches to Stop Hypertension (DASH) Eating Plan, to promote optimal health and reduce disease risk. A Mediterranean dietary pattern has also been promoted for health benefits. Our objective was to determine whether adherence to the USDA Food Guide recommendations, the DASH Eating Plan, or a Mediterranean dietary pattern is associated with reduced risk of distal colorectal adenoma. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, men and women aged 55-74 y were screened for colorectal cancer by sigmoidoscopy at 10 centers in the U.S. After adjusting for potential confounders, men who most complied with the USDA Food Guide recommendations had a 26% reduced risk of colorectal adenoma compared with men who least complied with the recommendations (OR USDA score >or= 5 vs. <or=2 = 0.74, 95% CI = 0.64-0.85; P-trend < 0.001). Comparable results were found for men who had intakes most similar to the DASH Eating Plan or a Mediterranean dietary pattern. Women who most complied with the USDA Food Guide recommendations had an 18% reduced risk for colorectal adenoma, but subgroup analyses revealed protective associations only for current smokers (OR USDA score >or= 5 vs. <or=2 = 0.52, 95% CI = 0.31-0.89; P-trend < 0.01) or normal-weight women (OR USDA score >or= 5 vs. <or=2 = 0.74, 95% CI = 0.55-0.99; P-trend = 0.08). Following the current U.S. dietary recommendations or a Mediterranean dietary pattern is associated with reduced risk of colorectal adenoma, especially in men
— id: 91688, year: 2007, vol: 137, page: 2443, stat: Journal Article,

Insulin resistance-related genes and advanced left-sided colorectal adenoma
Gunter, Marc J; Hayes, Richard B; Chatterjee, Nilanjan; Yeager, Meredith; Welch, Robert; Schoen, Robert E; Yakochi, Lance; Schatzkin, Arthur; Peters, Ulrike
2007 Apr;16(4):703-708, Cancer epidemiology biomarkers & prevention
BACKGROUND: Insulin resistance has been linked with colorectal neoplasia through a number of mechanistic and observational studies. Allelic variants of genes encoding components of the insulin pathway, including insulin (INS), insulin receptor (INSR), and insulin receptor substrate-1 and insulin receptor substrate-2 (IRS1 and IRS2) have been associated with hyperinsulinemia and insulin resistance and may, therefore, predict susceptibility to colorectal neoplasia. METHODS: We investigated whether single nucleotide polymorphisms (SNP) in the INS, INSR, IRS1, and IRS2 genes are associated with risk of advanced left-sided colorectal adenoma, a cancer precursor. We analyzed 20 SNPs in a largely Caucasian study population comprising 766 cases with advanced adenomas of the distal colon and 771 controls, all of whom had undergone flexible sigmoidoscopy as part of the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. RESULTS: Overall, we found limited evidence for a role of gene variants of the insulin signaling pathway and prevalence of advanced colorectal adenoma. We observed a statistically significant interaction between INSR genotypes and body mass index (BMI) with colorectal adenoma prevalence (P value for global test = 0.003) and suggestion of an interaction between INSR genotypes and glycemic load (P value for global test = 0.06); however, exploration of the interaction of BMI and glycemic load with the individual SNPs in INSR did not suggest a single SNP that may explain the significance of these global tests of interaction and did not yield any consistent patterns. CONCLUSION: These findings do not provide strong evidence for associations between polymorphic variation in genes of the insulin signaling pathway and advanced left-sided colorectal adenoma. Evidence for interaction between INSR variants and BMI and glycemic load for risk of advanced left-sided colorectal adenoma requires independent confirmation, and genotyping of INSR across a broader region and at greater density may be necessary to fully elucidate the nature of these interactions
— id: 91663, year: 2007, vol: 16, page: 703, stat: Journal Article,

Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women
Haiman, Christopher A; Dossus, Laure; Setiawan, V Wendy; Stram, Daniel O; Dunning, Alison M; Thomas, Gilles; Thun, Michael J; Albanes, Demetrius; Altshuler, David; Ardanaz, Eva; Boeing, Heiner; Buring, Julie; Burtt, Noel; Calle, Eugenia E; Chanock, Stephen; Clavel-Chapelon, Francoise; Colditz, Graham A; Cox, David G; Feigelson, Heather Spencer; Hankinson, Susan E; Hayes, Richard B; Henderson, Brian E; Hirschhorn, Joel N; Hoover, Robert; Hunter, David J; Kaaks, Rudolf; Kolonel, Laurence N; Le Marchand, Loic; Lenner, Per; Lund, Eiliv; Panico, Salvatore; Peeters, Petra H; Pike, Malcolm C; Riboli, Elio; Tjonneland, Anne; Travis, Ruth; Trichopoulos, Dimitrios; Wacholder, Sholom; Ziegler, Regina G
2007 Mar 1;67(5):1893-1897, Cancer research
The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the final step in the biosynthesis of estrogens. In this study, we used a systematic two-step approach that included gene resequencing and a haplotype-based analysis to comprehensively survey common genetic variation across the CYP19A1 locus in relation to circulating postmenopausal steroid hormone levels and breast cancer risk. This study was conducted among 5,356 invasive breast cancer cases and 7,129 controls comprised primarily of White women of European descent drawn from five large prospective cohorts within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A high-density single-nucleotide polymorphism (SNP) map of 103 common SNPs (> or =5% frequency) was used to identify the linkage disequilibrium and haplotype patterns across the CYP19A1 locus, and 19 haplotype-tagging SNPs were selected to provide high predictability of the common haplotype patterns. We found haplotype-tagging SNPs and common haplotypes spanning the coding and proximal 5' region of CYP19A1 to be significantly associated with a 10% to 20% increase in endogenous estrogen levels in postmenopausal women [effect per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 4.4 x 10(-15)]. No significant associations were observed, however, with these SNPs or common haplotypes and breast cancer risk. Thus, although genetic variation in CYP19A1 produces measurable differences in estrogen levels among postmenopausal women, the magnitude of the change was insufficient to contribute detectably to breast cancer
— id: 91659, year: 2007, vol: 67, page: 1893, stat: Journal Article,

Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium
Hashibe, Mia; Brennan, Paul; Benhamou, Simone; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Dal Maso, Luigino; Daudt, Alexander W; Fabianova, Eleonora; Fernandez, Leticia; Wunsch-Filho, Victor; Franceschi, Silvia; Hayes, Richard B; Herrero, Rolando; Koifman, Sergio; La Vecchia, Carlo; Lazarus, Philip; Levi, Fabio; Mates, Dana; Matos, Elena; Menezes, Ana; Muscat, Joshua; Eluf-Neto, Jose; Olshan, Andrew F; Rudnai, Peter; Schwartz, Stephen M; Smith, Elaine; Sturgis, Erich M; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Wei, Qingyi; Winn, Deborah M; Zaridze, David; Zatonski, Witold; Zhang, Zuo-Feng; Berthiller, Julien; Boffetta, Paolo
2007 May 16;99(10):777-789, Journal of the National Cancer Institute
BACKGROUND: At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. METHODS: We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10,244 head and neck cancer case subjects and 15,227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. RESULTS: Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. CONCLUSIONS: Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology
— id: 91667, year: 2007, vol: 99, page: 777, stat: Journal Article,

A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer
Hunter, David J; Kraft, Peter; Jacobs, Kevin B; Cox, David G; Yeager, Meredith; Hankinson, Susan E; Wacholder, Sholom; Wang, Zhaoming; Welch, Robert; Hutchinson, Amy; Wang, Junwen; Yu, Kai; Chatterjee, Nilanjan; Orr, Nick; Willett, Walter C; Colditz, Graham A; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Hayes, Richard B; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F Jr; Hoover, Robert N; Thomas, Gilles; Chanock, Stephen J
2007 Jul;39(7):870-874, Nature genetics
We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci
— id: 91669, year: 2007, vol: 39, page: 870, stat: Journal Article,

Human herpesvirus 8 seroprevalence among prostate cancer case patients and control subjects
Jenkins, F J; Hayes, R B; Jackson, A; Pizza, G; Mbisa, G; Whitby, D; Goedert, J J
2007 Jul 15;196(2):208-211, Journal of infectious diseases
To investigate a possible association between human herpesvirus 8 (HHV-8) and prostate cancer, we evaluated HHV-8 seroprevalence in 2 case-control studies. HHV-8 antibodies were detected by immunofluorescence with cells expressing lytic viral proteins and by enzyme immunoassays with recombinant viral structural protein (K8.1) and latent protein (latency-associated nuclear antigen-1; open reading frame 73), respectively. HHV-8 seroprevalence tended to be lower in patients with prostate cancer than in control subjects, but there was no significant difference in either study. These data imply that HHV-8 is not a major prevalent cause of prostate cancer
— id: 91673, year: 2007, vol: 196, page: 208, stat: Journal Article,

Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study
Kang, Daehee; Lee, Kyoung-Mu; Park, Sue Kyung; Berndt, Sonja I; Peters, Ulrike; Reding, Douglas; Chatterjee, Nilanjan; Welch, Robert; Chanock, Stephen; Huang, Wen-Yi; Hayes, Richard B
2007 Aug;16(8):1581-1586, Cancer epidemiology biomarkers & prevention
Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T>C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42; Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; P(trend) = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (>222; P(interaction) = 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (</=222) was stronger for smokers (OR, 1.44; 95% CI, 1.10-1.90). No significant association with prostate cancer was observed for polymorphic variants in SOD3 or SOD1. These results suggest that the Ala variant of SOD2 is associated with moderately increased risk of prostate cancer, particularly among men with lower intakes of dietary and supplemental vitamin E
— id: 91679, year: 2007, vol: 16, page: 1581, stat: Journal Article,

Lack of association of transforming growth factor-beta1 polymorphisms and haplotypes with prostate cancer risk in the prostate, lung, colorectal, and ovarian trial
Kang, Daehee; Lee, Kyoung-Mu; Park, Sue Kyung; Berndt, Sonja I; Reding, Douglas; Chatterjee, Nilanjan; Welch, Robert; Chanock, Stephen; Huang, Wen-Yi; Hayes, Richard B
2007 Jun;16(6):1303-1305, Cancer epidemiology biomarkers & prevention
— id: 91671, year: 2007, vol: 16, page: 1303, stat: Journal Article,

Prospective study of fruit and vegetable intake and risk of prostate cancer
Kirsh, Victoria A; Peters, Ulrike; Mayne, Susan T; Subar, Amy F; Chatterjee, Nilanjan; Johnson, Christine C; Hayes, Richard B
2007 Aug 1;99(15):1200-1209, Journal of the National Cancer Institute
BACKGROUND: Several epidemiologic studies have reported associations between fruit and vegetable intake and reduced risk of prostate cancer, but the findings are inconsistent and data on clinically relevant advanced prostate cancer are limited. METHODS: We evaluated the association between prostate cancer risk and intake of fruits and vegetables in 1338 patients with prostate cancer among 29,361 men (average follow-up = 4.2 years) in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Participants completed both a general risk factor and a 137-item food-frequency questionnaire at baseline. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Vegetable and fruit consumption was not related to prostate cancer risk overall; however, risk of extraprostatic prostate cancer (stage III or IV tumors) decreased with increasing vegetable intake (RR = 0.41, 95% CI = 0.22 to 0.74, for high versus low intake; P(trend) = .01). This association was mainly explained by intake of cruciferous vegetables (RR = 0.60, 95% CI = 0.36 to 0.98, for high versus low intake; P(trend) = .02), in particular, broccoli (RR = 0.55, 95% CI = 0.34 to 0.89, for >1 serving per week versus <1 serving per month; P(trend) = .02) and cauliflower (RR = 0.48, 95% CI = 0.25 to 0.89 for >1 serving per week versus <1 serving per month; P(trend) = .03). We found some evidence that risk of aggressive prostate cancer decreased with increasing spinach consumption, but the findings were not consistently statistically significant when restricted to extraprostatic disease. CONCLUSION: High intake of cruciferous vegetables, including broccoli and cauliflower, may be associated with reduced risk of aggressive prostate cancer, particularly extraprostatic disease
— id: 91680, year: 2007, vol: 99, page: 1200, stat: Journal Article,

Genotype frequency and F ST analysis of polymorphisms in immunoregulatory genes in Chinese and Caucasian populations
Lan, Qing; Shen, Min; Garcia-Rossi, Dino; Chanock, Stephen; Zheng, Tongzhang; Berndt, Sonja I; Puri, Vinita; Li, Guilan; He, Xingzhou; Welch, Robert; Zahm, Shelia H; Zhang, Luoping; Zhang, Yawei; Smith, Martyn; Wang, Sophia S; Chiu, Brian C-H; Linet, Martha; Hayes, Richard; Rothman, Nathaniel; Yeager, Meredith
2007 Nov;59(11):839-852, Immunogenetics
Selection and genetic drift can create genetic differences between populations. Cytokines and chemokines play an important role in both hematopoietic development and the inflammatory response. We compared the genotype frequencies of 45 SNPs in 30 cytokine and chemokine genes in two healthy Chinese populations and one Caucasian population. Several SNPs in IL4 had substantial genetic differentiation between the Chinese and Caucasian populations (F ST approximately 0.40), and displayed a strikingly different haplotype distribution. To further characterize common genetic variation in worldwide populations at the IL4 locus, we genotyped 9 SNPs at the IL4 gene in the Human Diversity Panel's (N = 1056) individuals from 52 world geographic regions. We observed low haplotype diversity, yet strikingly different haplotype frequencies between non-African populations, which may indicate different selective pressures on the IL4 gene in different parts of the world. SNPs in CSF2, IL6, IL10, CTLA4, and CX3CR1 showed moderate genetic differentiation between the Chinese and Caucasian populations (0.15 < F ST < 0.25). These results suggest that there is substantial genetic diversity in immune genes and exploration of SNP associations with immune-related diseases that vary in incidence across these two populations may be warranted
— id: 139004, year: 2007, vol: 59, page: 839, stat: Journal Article,

Genetic polymorphisms of NOS3 are associated with the risk of invasive breast cancer with lymph node involvement
Lee, Kyoung-Mu; Choi, Ji-Yeob; Lee, Jong Eun; Noh, Dong-Young; Ahn, Sei-Hyun; Han, Wonshik; Yoo, Keun-Young; Hayes, Richard B; Kang, Daehee
2007 Dec;106(3):433-438, Breast cancer research & treatment
Endothelial nitric oxide synthase (NOS3) produces nitric oxide which is a mediator of cytotoxic effects potentially associated with breast cancer. We evaluated the role of genetic polymorphisms of NOS3 in breast cancer etiology, in a case-control study conducted in Korea. We recruited 1,385 eligible patients with histologically confirmed incident breast cancer cases and 968 hospital-based controls. Two potentially functional NOS3 polymorphisms in the promoter region (-786T > C) and exon 7 (894G > T, Glu298Asp) were genotyped and individual haplotypes were estimated. Odds ratios (ORs) and 95% confidential intervals (95% CIs) were calculated by unconditional logistic regression, adjusting for age, body mass index, education, family history of breast cancer in first and second degree relatives, age at first full-term pregnancy and parity. There was no overall association between the -786T > C or 894G > T genotype and breast cancer risk. However, the -786C allele was marginally associated with decreased risk for invasive breast cancer with lymph node involvement (OR = 0.76, 95% CI = 0.56-1.04). And, compared to TG-TG carriers, all other haplotype pairs were significantly associated with invasive breast cancer with lymph node involvement (OR = 0.77, 95% CI = 0.59-0.99). Our results suggest that genetic polymorphisms in NOS3 modify individual susceptibility to invasive breast cancer with lymph node involvement in Korean women
— id: 91656, year: 2007, vol: 106, page: 433, stat: Journal Article,

The impact of an alien plant on a native plant-pollinator network: an experimental approach
Lopezaraiza-Mikel, Martha E; Hayes, Richard B; Whalley, Martin R; Memmott, Jane
2007 Jul;10(7):539-550, Ecology letters
Studies of pairwise interactions have shown that an alien plant can affect the pollination of a native plant, this effect being mediated by shared pollinators. Here we use a manipulative field experiment, to investigate the impact of the alien plant Impatiens glandulifera on an entire community of coflowering native plants. Visitation and pollen transport networks were constructed to compare replicated I. glandulifera invaded and I. glandulifera removal plots. Invaded plots had significantly higher visitor species richness, visitor abundance and flower visitation. However, the pollen transport networks were dominated by alien pollen grains in the invaded plots and consequently higher visitation may not translate in facilitation for pollination. The more generalized insects were more likely to visit the alien plant, and Hymenoptera and Hemiptera were more likely to visit the alien than Coleoptera. Our data indicate that generalized native pollinators can provide a pathway of integration for alien plants into native visitation systems
— id: 91670, year: 2007, vol: 10, page: 539, stat: Journal Article,

Cigarette smoking and cancer risk: modeling total exposure and intensity
Lubin, Jay H; Alavanja, Michael C R; Caporaso, Neil; Brown, Linda M; Brownson, Ross C; Field, R William; Garcia-Closas, Montserrat; Hartge, Patricia; Hauptmann, Michael; Hayes, Richard B; Kleinerman, Ruth; Kogevinas, Manolis; Krewski, Daniel; Langholz, Bryan; Letourneau, Ernest G; Lynch, Charles F; Malats, Nuria; Sandler, Dale P; Schaffrath-Rosario, Angelika; Schoenberg, Janet B; Silverman, Debra T; Wang, Zuoyuan; Wichmann, H-Erich; Wilcox, Homer B; Zielinski, Jan M
2007 Aug 15;166(4):479-489, American journal of epidemiology
A recent analysis showed that the excess odds ratio (EOR) for lung cancer due to smoking can be modeled by a function which is linear in total pack-years and exponential in the logarithm of smoking intensity and its square. Below 15-20 cigarettes per day, the EOR/pack-year increased with intensity (direct exposure rate or enhanced potency effect), suggesting greater risk for a total exposure delivered at higher intensity (for a shorter duration) than for an equivalent exposure delivered at lower intensity. Above 20 cigarettes per day, the EOR/pack-year decreased with increasing intensity (inverse exposure rate or reduced potency effect), suggesting greater risk for a total exposure delivered at lower intensity (for a longer duration) than for an equivalent exposure delivered at higher intensity. The authors applied this model to data from 10 case-control studies of cancer, including cancers of the lung, bladder, oral cavity, pancreas, and esophagus. At lower intensities, there was enhanced potency for several cancer sites, but narrow ranges for pack-years increased uncertainty, precluding definitive conclusions. At higher intensities, there was a consistent reduced potency effect across studies. The intensity effects were statistically homogeneous, indicating that after accounting for risk from total pack-years, intensity patterns were comparable across the diverse cancer sites
— id: 91672, year: 2007, vol: 166, page: 479, stat: Journal Article,

Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer screening trial
Millen, Amy E; Subar, Amy F; Graubard, Barry I; Peters, Ulrike; Hayes, Richard B; Weissfeld, Joel L; Yokochi, Lance A; Ziegler, Regina G
2007 Dec;86(6):1754-1764, American journal of clinical nutrition
BACKGROUND: Research on the association between fruit and vegetable intake and risk of colorectal adenoma is inconclusive. OBJECTIVE: We studied whether intake of fruit, vegetables, or their subgroups is associated with a lower risk of prevalent colorectal adenoma. DESIGN: In men and women (aged 55-74 y) who were screened for colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (1993-2001), we compared 3,057 cases with at least one prevalent histologically verified adenoma of the distal large bowel with 29,413 control subjects. Using a food-frequency questionnaire, we quantified intake of fruit and vegetables in the 12 mo before screening as energy-adjusted pyramid servings/d (ps/d). Adjusted odds ratios (ORs) and 95% CIs were estimated by logistic regression. RESULTS: Risk of distal adenoma was significantly lower among subjects in high (approximately 5.7 ps/d) versus low (approximately 1.2 ps/d) quintiles of total fruit intake (OR: 0.75; 95% CI: 0.66, 0.86, P for trend <0.001), which was not completely explained by dietary folate or fiber intake. Inverse associations between adenoma and total fruit intake were observed regardless of adenoma histopathology and multiplicity. However, the protective effect was seen only for colon and not rectal adenoma. Total vegetable intake was not significantly associated with reduced risk of adenoma. ORs for colorectal adenoma among persons with high versus low intakes of deep-yellow vegetables, dark-green vegetables, and onions and garlic were significantly related to lower risk of adenoma, although the P for trend for dark-green vegetables was not significant. CONCLUSION: Diets rich in fruit and deep-yellow vegetables, dark-green vegetables, and onions and garlic are modestly associated with reduced risk of colorectal adenoma, a precursor of colorectal cancer
— id: 91692, year: 2007, vol: 86, page: 1754, stat: Journal Article,

Serum selenium and risk of prostate cancer-a nested case-control study
Peters, Ulrike; Foster, Charles B; Chatterjee, Nilanjan; Schatzkin, Arthur; Reding, Douglas; Andriole, Gerald L; Crawford, E David; Sturup, Stefan; Chanock, Stephen J; Hayes, Richard B
2007 Jan;85(1):209-217, American journal of clinical nutrition
BACKGROUND: Selenium is a potential chemopreventive agent against prostate cancer, whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes. Interrelations with other antioxidative agents and oxidative stressors, such as smoking, are poorly understood. OBJECTIVES: The aims were to investigate the association between serum selenium and prostate cancer risk and to examine interactions with other antioxidants and tobacco use. DESIGN: A nested case-control study was performed within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum selenium in prospectively collected samples was compared between 724 incident prostate cancer case subjects and 879 control subjects, frequency-matched for age, time since initial screen, and year of blood draw. The men were followed for up to 8 y. RESULTS: Overall, serum selenium was not associated with prostate cancer risk (P for trend = 0.70); however, higher serum selenium was associated with lower risks in men reporting a high (more than the median: 28.0 IU/d) vitamin E intake [odds ratio (OR) for the highest compared with the lowest quartile of selenium: 0.58; 95% CI: 0.37, 0.91; P for trend = 0.05; P for interaction = 0.01] and in multivitamin users (OR for highest compared with the lowest quartile of selenium: 0.61; 95% CI: 0.36, 1.04; P for trend = 0.06; P for interaction = 0.05). Furthermore, among smokers, high serum selenium concentrations were related to reduced prostate cancer risk (OR for the highest compared with the lowest quartile of selenium: 0.65; 95% CI: 0.44, 0.97; P for trend = 0.09; P for interaction = 0.007). CONCLUSION: Greater prediagnostic serum selenium concentrations were not associated with prostate cancer risk in this large cohort, although greater concentrations were associated with reduced prostate cancer risks in men who reported a high intake of vitamin E, in multivitamin users, and in smokers
— id: 91653, year: 2007, vol: 85, page: 209, stat: Journal Article,

Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial
Peters, Ulrike; Leitzmann, Michael F; Chatterjee, Nilanjan; Wang, Yinghui; Albanes, Demetrius; Gelmann, Edward P; Friesen, Marlin D; Riboli, Elio; Hayes, Richard B
2007 May;16(5):962-968, Cancer epidemiology biomarkers & prevention
BACKGROUND: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer-preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive. MATERIALS AND METHODS: We investigated the association between prediagnostic serum carotenoids (lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score >or=7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under non-trial conditions. RESULTS: No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). beta-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk. CONCLUSION: In this large prospective study, high serum beta-carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention
— id: 91668, year: 2007, vol: 16, page: 962, stat: Journal Article,

Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial
Pinsky, P F; Miller, A; Kramer, B S; Church, T; Reding, D; Prorok, P; Gelmann, E; Schoen, R E; Buys, S; Hayes, R B; Berg, C D
2007 Apr 15;165(8):874-881, American journal of epidemiology
Volunteers for prevention or screening trials are generally healthier and have lower mortality than the general population. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) is an ongoing, multicenter, randomized trial that randomized 155,000 men and women aged 55-74 years to a screening or control arm between 1993 and 2001. The authors compared demographics, mortality rates, and cancer incidence and survival rates of PLCO subjects during the early phase of the trial with those of the US population. Incidence and mortality from PLCO cancers (prostate, lung, colorectal, and ovarian) were excluded because they are the subject of the ongoing trial. Standardized mortality ratios for all-cause mortality were 46 for men, 38 for women, and 43 overall (100 = standard). Cause-specific standardized mortality ratios were 56 for cancer, 37 for cardiovascular disease, and 34 for both respiratory and digestive diseases. Standardized mortality ratios for all-cause mortality increased with time on study from 31 at year 1 to 48 at year 7. Adjusting the PLCO population to a standardized demographic distribution would increase the standardized mortality ratio only modestly to 54 for women and 55 for men. Standardized incidence ratios for all cancer were 84 in women and 73 in men, with a large range of standardized incidence ratios observed for specific cancers
— id: 91655, year: 2007, vol: 165, page: 874, stat: Journal Article,

A common 8q24 variant in prostate and breast cancer from a large nested case-control study
Schumacher, Fredrick R; Feigelson, Heather Spencer; Cox, David G; Haiman, Christopher A; Albanes, Demetrius; Buring, Julie; Calle, Eugenia E; Chanock, Stephen J; Colditz, Graham A; Diver, W Ryan; Dunning, Alison M; Freedman, Matthew L; Gaziano, John M; Giovannucci, Edward; Hankinson, Sue E; Hayes, Richard B; Henderson, Brian E; Hoover, Robert N; Kaaks, Rudolf; Key, Timothy; Kolonel, Laurence N; Kraft, Peter; Le Marchand, Loic; Ma, Jing; Pike, Malcolm C; Riboli, Elio; Stampfer, Meir J; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Travis, Ruth; Virtamo, Jarmo; Andriole, Gerald; Gelmann, Edward; Willett, Walter C; Hunter, David J
2007 Apr 1;67(7):2951-2956, Cancer research
Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rs1447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 x 10(-13)). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 x 10(-13)). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an OR(AC) = 1.34 (99% confidence intervals, 1.19-1.50) and carriers with two copies of the minor allele had an OR(AA) = 1.86 (99% confidence intervals, 1.30-2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result
— id: 91662, year: 2007, vol: 67, page: 2951, stat: Journal Article,

CYP17 genetic variation and risk of breast and prostate cancer from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
Setiawan, Veronica Wendy; Schumacher, Fredrick R; Haiman, Christopher A; Stram, Daniel O; Albanes, Demetrius; Altshuler, David; Berglund, Goran; Buring, Julie; Calle, Eugenia E; Clavel-Chapelon, Francoise; Cox, David G; Gaziano, J Michael; Hankinson, Susan E; Hayes, Richard B; Henderson, Brian E; Hirschhorn, Joel; Hoover, Robert; Hunter, David J; Kaaks, Rudolf; Kolonel, Laurence N; Kraft, Peter; Ma, Jing; Le Marchand, Loic; Linseisen, Jakob; Lund, Eiliv; Navarro, Carmen; Overvad, Kim; Palli, Domenico; Peeters, Petra H M; Pike, Malcolm C; Riboli, Elio; Stampfer, Meir J; Thun, Michael J; Travis, Ruth; Trichopoulos, Dimitrios; Yeager, Meredith; Ziegler, Regina G; Spencer Feigelson, Heather; Chanock, Stephen J
2007 Nov;16(11):2237-2246, Cancer epidemiology biomarkers & prevention
CYP17 encodes cytochrome p450c17alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R(h)(2) >or= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% CI), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend=0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend=0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend=0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend=0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility
— id: 91690, year: 2007, vol: 16, page: 2237, stat: Journal Article,

Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial
Wang, Sophia S; Morton, Lindsay M; Bergen, Andrew W; Lan, Elizabeth Z; Chatterjee, Nilanjan; Kvale, Paul; Hayes, Richard B; Chanock, Stephen J; Caporaso, Neil E
2007 Aug;122(1):41-49, Human genetics
Catechol-O-methyltransferase (COMT) is an important modulator in the catabolism of extraneural dopamine, which plays an important role in drug reward mechanisms. It is hypothesized that genetic variations in the COMT gene, which can result in a three to fourfold difference in COMT enzyme activity, may be associated with several reward-motivated behaviors. The aim of our study was to examine the relationship between COMT polymorphisms with smoking, obesity and alcohol. Three single nucleotide polymorphisms (SNPs) in COMT were genotyped in 2,371 participants selected randomly from the screening arm of the PLCO Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. SNP and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from conditional logistic regression models, adjusted for race/ethnicity. The COMT Ex4-76C > G (Leu136Leu) polymorphism was statistically significantly associated with individuals who had >30% increases in BMI from ages 20 to 50 years, compared to those with 0-5% increase in BMI (0-5%) over the same age period: (CC is referent; OR(CG )= 1.42, OR(GG )= 1.46, P (trend )= 0.06). By sex, the increased risk was further pronounced among females (OR(CG )= 1.50, OR(GG )= 2.10, P (trend )= 0.03). Consistent with our analyses of single polymorphisms, individuals whose BMI increased >30% from ages 20 to 50 years were more likely than individuals with 0-5% increases in BMI to possess COMT haplotypes [COMT Ex3-104C > T-COMT Ex4-76 C > G-COMT Ex4-12 A > G] that included the variant allele for COMT Ex4-76 C > G: C-G-G (T-C-A is referent: OR(C-G-G )= 1.33, 95% CI 1.01-1.77) and C-G-A (OR(C-G-A )= 1.79, 95% CI 0.72-4.49). We observed no association between any of the COMT polymorphisms with smoking behavior or alcohol intake. The COMT Ex4-76C > G (Leu136Leu) polymorphism appears to play a role in large increases in BMI. The null association with smoking and alcohol and the pronounced association with increasing BMI among women further implicates COMT's role in estrogen metabolism as a potentially culpable pathway. Our results support a need for comprehensive evaluation of COMT variations and their functional relevance as COMT may be an important molecular target to evaluate for new treatments regarding obesity
— id: 91665, year: 2007, vol: 122, page: 41, stat: Journal Article,

IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
Weiss, Jocelyn M; Huang, Wen-Yi; Rinaldi, Sabina; Fears, Thomas R; Chatterjee, Nilanjan; Chia, David; Crawford, E David; Kaaks, Rudolf; Hayes, Richard B
2007 Nov 15;121(10):2267-2273, International journal of cancer
IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men
— id: 91677, year: 2007, vol: 121, page: 2267, stat: Journal Article,

Genome-wide association study of prostate cancer identifies a second risk locus at 8q24
Yeager, Meredith; Orr, Nick; Hayes, Richard B; Jacobs, Kevin B; Kraft, Peter; Wacholder, Sholom; Minichiello, Mark J; Fearnhead, Paul; Yu, Kai; Chatterjee, Nilanjan; Wang, Zhaoming; Welch, Robert; Staats, Brian J; Calle, Eugenia E; Feigelson, Heather Spencer; Thun, Michael J; Rodriguez, Carmen; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Giovannucci, Edward; Willett, Walter C; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Gelmann, Edward P; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F Jr; Hoover, Robert; Hunter, David J; Chanock, Stephen J; Thomas, Gilles
2007 May;39(5):645-649, Nature genetics
Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%)
— id: 91660, year: 2007, vol: 39, page: 645, stat: Journal Article,

Aberrations in chromosomes associated with lymphoma and therapy-related leukemia in benzene-exposed workers
Zhang, Luoping; Rothman, Nathaniel; Li, Guilan; Guo, Weihong; Yang, Wei; Hubbard, Alan E; Hayes, Richard B; Yin, Songnian; Lu, Wei; Smith, Martyn T
2007 Jul;48(6):467-474, Environmental & molecular mutagenesis
Epidemiological studies show that benzene exposure is associated with an increased incidence of leukemia and perhaps lymphoma. Chromosomal rearrangements are common in these hematopoietic diseases. Translocation t(14;18), the long-arm deletion of chromosome 6 [del(6q)], and trisomy 12 are frequently observed in lymphoma patients. Rearrangements of the MLL gene located on chromosome 11q23, such as t(4;11) and t(6;11), are common in therapy-related leukemias resulting from treatment with topoisomerase II inhibiting drugs. To examine numerical and structural changes in these chromosomes (2, 4, 6, 11, 12, 14, and 18), fluorescence in situ hybridization (FISH) was employed on metaphase spreads from workers exposed to benzene (n = 43) and matched controls (n = 44) from Shanghai, China. Aneuploidy (both monosomy and trisomy) of all seven chromosomes was increased by benzene exposure. Benzene also induced del(6q) in a dose-dependent manner (P(trend) = 0.0002). Interestingly, translocations between chromosomes 14 and 18, t(14;18), known to be associated with follicular non-Hodgkin lymphoma, were increased in the highly exposed workers (P < 0.001). On the other hand, translocations between chromosome 11 and other partner chromosomes that are found in therapy-induced leukemias were not increased. These data add weight to the notion that benzene can induce t(14;18) and del(6q) found in lymphoma, but do not support the idea that benzene induces t(4;11) or t(6;11). However, they do not rule out the possibility that other rearrangements of the MLL gene at chromosome 11q23 may be induced by benzene
— id: 91675, year: 2007, vol: 48, page: 467, stat: Journal Article,

NAT2 slow acetylation and bladder cancer in workers exposed to benzidine
Carreon, Tania; Ruder, Avima M; Schulte, Paul A; Hayes, Richard B; Rothman, Nathaniel; Waters, Martha; Grant, Delores J; Boissy, Robert; Bell, Douglas A; Kadlubar, Fred F; Hemstreet, George P 3rd; Yin, Songnian; LeMasters, Grace K
2006 Jan 1;118(1):161-168, International journal of cancer
This study expands a previous study of NAT2 polymorphisms and bladder cancer in male subjects occupationally exposed only to benzidine. The combined analysis of 68 cases and 107 controls from a cohort of production workers in China exposed to benzidine included 30 new cases and 67 controls not previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. PCR-based methods identified genotypes for NAT2, NAT1 and GSTM1. NAT2 phenotype and genotype data were consistent. A protective association was observed for the slow NAT2 genotype (bladder cancer OR = 0.3; 95% CI = 0.1 = 1.0) after adjustment for cumulative benzidine exposure and lifetime smoking. Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8, 95% CI = 0.8-10.1 and OR = 2.2, 95% CI = 0.6-8.3, respectively). No association was found between GSTM1 null and bladder cancer. A metaanalysis risk estimate of case-control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators. The lower limit of the confidence interval (OR = 1.4; 95% CI = 1.0-2.0) approximated the upper confidence interval for the estimate obtained in our analysis. These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine-exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2-naphthylamine and 4-aminobiphenyl. Study findings suggest the existence of key differences in the metabolism of mono- and diarylamines
— id: 91617, year: 2006, vol: 118, page: 161, stat: Journal Article,

Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer
Choi, Ji-Yeob; Lee, Kyoung-Mu; Noh, Dong-Young; Ahn, Sei-Hyun; Lee, Jong-Eun; Han, Wonshik; Jang, In-Jin; Shin, Sang-Goo; Yoo, Keun-Young; Hayes, Richard B; Kang, Daehee
2006 Nov;100(2):213-218, Breast cancer research & treatment
The endothelial cell-specific form of nitric oxide synthase (eNOS) may play an important role in tumor progression via angiogenesis or apoptosis. We studied eNOS -786T > C and 894G > T (Glu298Asp), two functionally significant SNPs, in relation to hazard of breast cancer recurrence or death in 873 women with incident, non-metastatic breast cancer, recruited from two teaching hospitals in Seoul, Korea, 1995-2002. Hazards were estimated by Cox proportional hazard models, in relation to genotype, adjusting for hormone receptor status, lymph node involvement, and tumor size. Women carriers of the eNOS -786C allele had significantly increased hazards of breast cancer recurrence or death, compared with women having the TT genotype (HR = 2.1, 95% CI = 1.03-4.33); risks increased up to 3-fold in ER positive cases (HR = 3.2, 95% CI = 0.95-10.50). The hazard was also increased in eNOS 894T carriers, however, it did not reach statistical significance (HR = 1.8, 95% CI = 0.85-3.93). The combined genotypes containing -786C or 894T was associated with a 2.5-fold risk, compared to the TT-GG genotypes, the most dominant genotype combination (95% CI = 1.29-4.68), with the greatest risks in ER positive cases (HR = 4.9, 95% CI = 1.31-18.36). These results indicate that the eNOS -786C polymorphism, and possibly the 894T polymorphism, are associated with breast cancer recurrence and death, particularly in women with ER positive tumors
— id: 91642, year: 2006, vol: 100, page: 213, stat: Journal Article,

Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies
Feigelson, Heather Spencer; Cox, David G; Cann, Howard M; Wacholder, Sholom; Kaaks, Rudolf; Henderson, Brian E; Albanes, Demetrius; Altshuler, David; Berglund, Goran; Berrino, Franco; Bingham, Sheila; Buring, Julie E; Burtt, Noel P; Calle, Eugenia E; Chanock, Stephen J; Clavel-Chapelon, Francoise; Colditz, Graham; Diver, W Ryan; Freedman, Matthew L; Haiman, Christopher A; Hankinson, Susan E; Hayes, Richard B; Hirschhorn, Joel N; Hunter, David; Kolonel, Laurence N; Kraft, Peter; LeMarchand, Loic; Linseisen, Jakob; Modi, William; Navarro, Carmen; Peeters, Petra H; Pike, Malcolm C; Riboli, Elio; Setiawan, V Wendy; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Tjonneland, Anne; Trichopoulos, Dimitrios
2006 Feb 15;66(4):2468-2475, Cancer research
The 17beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) encodes 17HSD1, which catalyzes the final step of estradiol biosynthesis. Despite the important role of HSD17B1 in hormone metabolism, few epidemiologic studies of HSD17B1 and breast cancer have been conducted. This study includes 5,370 breast cancer cases and 7,480 matched controls from five large cohorts in the Breast and Prostate Cancer Cohort Consortium. We characterized variation in HSD17B1 by resequencing and dense genotyping a multiethnic sample and identified haplotype-tagging single nucleotide polymorphisms (htSNP) that capture common variation within a 33.3-kb region around HSD17B1. Four htSNPs, including the previously studied SNP rs605059 (S312G), were genotyped to tag five common haplotypes in all cases and controls. Conditional logistic regression was used to estimate odds ratios (OR) for disease. We found no evidence of association between common HSD17B1 haplotypes or htSNPs and overall risk of breast cancer. The OR for each haplotype relative to the most common haplotype ranged from 0.98 to 1.07 (omnibus test for association: X2 = 3.77, P = 0.58, 5 degrees of freedom). When cases were subdivided by estrogen receptor (ER) status, two common haplotypes were associated with ER-negative tumors (test for trend, Ps = 0.0009 and 0.0076; n = 353 cases). HSD17B1 variants that are common in Caucasians are not associated with overall risk of breast cancer; however, there was an association among the subset of ER-negative tumors. Although the probability that these ER-negative findings are false-positive results is high, these findings were consistent across each cohort examined and warrant further study
— id: 91635, year: 2006, vol: 66, page: 2468, stat: Journal Article,

Carbohydrate, glycemic index, and glycemic load and colorectal adenomas in the Prostate, Lung, Colorectal, and Ovarian Screening Study
Flood, Andrew; Peters, Ulrike; Jenkins, David J A; Chatterjee, Nilanjan; Subar, Amy F; Church, Timothy R; Bresalier, Robert; Weissfeld, Joel L; Hayes, Richard B; Schatzkin, Arthur
2006 Nov;84(5):1184-1192, American journal of clinical nutrition
BACKGROUND: It is possible that high-glycemic-load diets, through their hyperinsulinemic effects, can increase the risk of colorectal cancer. OBJECTIVE: We analyzed data from a cancer screening study to determine whether persons with high-glycemic-load diets would be at an increased risk of distal adenomas. DESIGN: We included subjects with no prior adenoma or cancer from the Prostate, Lung, Colorectal, and Ovarian screening trial and whose results from flexible sigmoidoscopy exams indicated either no lesions (n = 34 817) or >/=1 distal adenoma (n = 3696). We used a 137-item food-frequency questionnaire to assess usual dietary intake over the preceding 12 mo. Using logistic regression analysis, we calculated, separately for men and women, prevalence odds ratios (ORs) and 95% CIs of sigmoidoscopy-detected, distal adenomas for quintiles of energy-adjusted dietary carbohydrate, glycemic index, and glycemic load. RESULTS: ORs decreased with increasing intakes of carbohydrate for both the men and the women in unadjusted models, but these associations were attenuated in multivariate-adjusted models. Among the men, the association remained significant after adjustment (OR: 0.71; 95% CI 0.60, 0.84; P for trend < 0.0001), but in the women it did not (OR: 0.89; 95% CI: 0.73, 1.10; P for trend = 0.30). The results for glycemic index showed no associations in either men or women. Results for glycemic load closely mirrored those for carbohydrate. CONCLUSION: Despite expectations that increasing glycemic load and glycemic index would increase the risk of adenoma, we observed no association in women and even an inverse association in men
— id: 91650, year: 2006, vol: 84, page: 1184, stat: Journal Article,

Nucleotide excision repair gene polymorphisms and risk of advanced colorectal adenoma: XPC polymorphisms modify smoking-related risk
Huang, Wen-Yi; Berndt, Sonja I; Kang, Daehee; Chatterjee, Nilanjan; Chanock, Stephen J; Yeager, Meredith; Welch, Robert; Bresalier, Robert S; Weissfeld, Joel L; Hayes, Richard B
2006 Feb;15(2):306-311, Cancer epidemiology biomarkers & prevention
OBJECTIVES: Nucleotide excision repair enzymes remove bulky damage caused by environmental agents, including carcinogenic polycyclic aromatic hydrocarbons found in cigarette smoke, a risk factor for colorectal adenoma. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we studied the risk of advanced colorectal adenoma in relation to cigarette smoking and selected single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway.METHODS: Cases (n = 772) were subjects with left-sided advanced adenoma (>1 cm in size, high-grade dysplasia, or villous characteristics). Controls (n = 777) were screen-negative for left-sided polyps by sigmoidoscopy. DNA was extracted from blood samples and 15 common nonsynonymous SNPs in seven-nucleotide excision repair genes [XPC, RAD23B (hHR23B), CSB (ERCC6), XPD (ERCC2), CCNH, XPF (ERCC4), and XPG (ERCC5)] were genotyped.RESULTS: None of the studied SNPs were independently associated with advanced adenoma risk. Smoking was related to adenoma risk and XPC polymorphisms (R492H, A499V, K939Q) modified these effects (P(interaction) from 0.03-0.003). Although the three XPC variants were in linkage disequilibrium, a multivariate logistic regression tended to show independent protective effects for XPC 499V (P(trend) = 0.06), a finding supported by haplotype analysis (covariate-adjusted global permutation P = 0.03).CONCLUSIONS: Examining a spectrum of polymorphic variants in nucleotide excision repair genes, we found evidence that smoking-associated risks for advanced colorectal adenoma are modified by polymorphisms in XPC, particularly haplotypes containing XPC 499V
— id: 91636, year: 2006, vol: 15, page: 306, stat: Journal Article,

Tobacco smoking and colorectal hyperplastic and adenomatous polyps
Ji, Bu-Tian; Weissfeld, Joel L; Chow, Wong-Ho; Huang, Wen-Yi; Schoen, Robert E; Hayes, Richard B
2006 May;15(5):897-901, Cancer epidemiology biomarkers & prevention
Colorectal adenomas and possibly some hyperplastic polyps are precursors of colorectal cancer. Tobacco use is associated in epidemiologic studies with these polyps, although links between smoking and colorectal cancer are less consistent. To characterize the role of tobacco in early colorectal carcinogenesis, we compared tobacco use among 4,383 subjects with histologically verified benign (hyperplastic or adenomatous) polyps of the distal colon (descending colon, sigmoid, and rectum) with tobacco use among 33,667 subjects who were endoscopy negative for distal colon tumors, in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Trial, a randomized trial of flexible sigmoidoscopy. Risks, estimated by the odds ratio (OR), associated with current cigarette use were OR = 4.4 [95% confidence interval (95% CI), 3.7-5.2] for hyperplastic polyps only, OR = 1.8 (95% CI, 1.5-2.1) for adenomas only, and OR = 6.2 (95% CI, 4.7-8.3) for subjects with both hyperplastic and adenomatous polyps concurrently. Effects were weaker among ex smokers; the smoking-associated ORs remained consistently higher for hyperplastic polyps. This pattern was also seen in relation to cigarettes smoked per day, smoking duration, and pack-years. Tobacco-associated risks for multiple polyps were also stronger when hyperplastic disease was involved. In conclusion, tobacco use, particularly recent use, increases risk for both adenomatous and hyperplastic polyps, but the risks are substantially greater for hyperplastic lesions
— id: 91639, year: 2006, vol: 15, page: 897, stat: Journal Article,

Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk
Kirsh, Victoria A; Hayes, Richard B; Mayne, Susan T; Chatterjee, Nilanjan; Subar, Amy F; Dixon, L Beth; Albanes, Demetrius; Andriole, Gerald L; Urban, Donald A; Peters, Ulrike
2006 Feb 15;98(4):245-254, Journal of the National Cancer Institute
BACKGROUND: Vitamin E, beta-carotene, and vitamin C are micronutrient antioxidants that protect cells from oxidative damage involved in prostate carcinogenesis. In separate trials, supplemental vitamin E was associated with a decreased risk of prostate cancer among smokers and supplemental beta-carotene was associated with a decreased risk of prostate cancer among men with low baseline plasma beta-carotene levels. METHODS: We evaluated the association between intake of these micronutrient antioxidants from foods and supplements and the risk of prostate cancer among men in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. At baseline, trial participants completed a 137-item food frequency questionnaire that included detailed questions on 12 individual supplements. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: We identified 1338 cases of prostate cancer among 29 361 men during up to 8 years of follow-up. Overall, there was no association between prostate cancer risk and dietary or supplemental intake of vitamin E, beta-carotene, or vitamin C. However, among current and recent (i.e., within the previous 10 years) smokers, decreasing risks of advanced prostate cancer (i.e., Gleason score > or = 7 or stage III or IV) were associated with increasing dose (RR for > 400 IU/day versus none = 0.29, 95% CI = 0.12 to 0.68; Ptrend = .01) and duration (RR for > or = 10 years of use versus none = 0.30, 95% CI = 0.09 to 0.96; Ptrend = .01) of supplemental vitamin E use. Supplemental beta-carotene intake at a dose level of at least 2000 microg/day was associated with decreased prostate cancer risk in men with low (below the median of 4129 microg/day) dietary beta-carotene intake (RR = 0.52, 95% CI = 0.33 to 0.81). Among smokers, the age-adjusted rate of advanced prostate cancer was 492 per 100,000 person-years in those who did not take supplemental vitamin E, 153 per 100,000 person-years in those who took more than 400 IU/day of supplemental vitamin E, and 157 per 100,000 person-years in those who took supplemental vitamin E for 10 or more years. Among men with low dietary beta-carotene intake, the age-adjusted rate of prostate cancer was 1122 per 100,000 person-years in those who did not take supplemental beta-carotene, and 623 per 100,000 person-years in those who took at least 2000 microg/day of supplemental beta-carotene. CONCLUSIONS: Our results do not provide strong support for population-wide implementation of high-dose antioxidant supplementation for the prevention of prostate cancer. However, vitamin E supplementation in male smokers and beta-carotene supplementation in men with low dietary beta-carotene intakes were associated with reduced risk of this disease
— id: 91634, year: 2006, vol: 98, page: 245, stat: Journal Article,

A prospective study of lycopene and tomato product intake and risk of prostate cancer
Kirsh, Victoria A; Mayne, Susan T; Peters, Ulrike; Chatterjee, Nilanjan; Leitzmann, Michael F; Dixon, L Beth; Urban, Donald A; Crawford, E David; Hayes, Richard B
2006 Jan;15(1):92-98, Cancer epidemiology biomarkers & prevention
BACKGROUND: Dietary lycopene and tomato products may reduce risk of prostate cancer; however, uncertainty remains about this possible association.METHODS: We evaluated the association between intake of lycopene and specific tomato products and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to investigate cancer early detection methods and etiologic determinants. Participants completed both a general risk factor and a 137-item food frequency questionnaire at baseline. A total of 1,338 cases of prostate cancer were identified among 29,361 men during an average of 4.2 years of follow-up.RESULTS: Lycopene intake was not associated with prostate cancer risk. Reduced risks were also not found for total tomato servings or for most tomato-based foods. Statistically nonsignificant inverse associations were noted for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.67-1.03 for >or=1 serving/wk versus < 0.5 serving/mo; P(trend)=0.06 and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; P(trend)=0.12] and spaghetti/tomato sauce consumption (advanced prostate cancer: RR=0.81, 95% CI, 0.57-1.16 for >or=2 servings/wk versus<1 serving/mo; P(trend)=0.31). Among men with a family history of prostate cancer, risks were decreased in relation to increased consumption of lycopene (P(trend)=0.04) and specific tomato-based foods commonly eaten with fat (spaghetti, P(trend)=0.12; pizza, P(trend)=0.15; lasagna, P(trend)=0.02).CONCLUSIONS: This large study does not support the hypothesis that greater lycopene/tomato product consumption protects from prostate cancer. Evidence for protective associations in subjects with a family history of prostate cancer requires further corroboration
— id: 91632, year: 2006, vol: 15, page: 92, stat: Journal Article,

Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk of prostate cancer
Michaud, Dominique S; Daugherty, Sarah E; Berndt, Sonja I; Platz, Elizabeth A; Yeager, Meredith; Crawford, E David; Hsing, Ann; Huang, Wen-Yi; Hayes, Richard B
2006 Apr 15;66(8):4525-4530, Cancer research
Chronic intraprostatic inflammation is suspected to play a role in the pathogenesis of prostate cancer. Polymorphisms in cytokine genes can influence inflammation and immune response and may be related to the risk of prostate cancer. Four common single nucleotide polymorphisms (SNPs) in the genes encoding interleukin-1B (IL-1B), IL-6, and IL-8 were assessed in 503 prostate cancer cases and 652 controls, and three SNPs in IL-10 were assessed in an additional 817 prostate cancer cases and 1,190 controls (for a total of 1,320 prostate cancer cases and 1,255 controls). Cases and controls were selected from the on-going Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial and were frequency matched on age, ethnicity, time-period since initial screening, and date of blood draw. Single-locus analyses were conducted using conditional logistic regression. In addition, we did a haplotype analysis for the three IL-10 SNPs tested. Overall, no associations were detected between the seven polymorphisms in the four cytokine genes examined in this study and prostate cancer risk. Further stratifying by use of nonsteroidal anti-inflammatory drugs did not modify the associations. Findings were similar for early or advanced prostate cancers. Similarly, we observed no association between the major IL-10 haplotypes and the risk of prostate cancer. At least seven common polymorphisms in genes of inflammatory cytokines IL-1B, IL-6, IL-8, and IL-10 do not seem to play a role in the risk of prostate cancer
— id: 91638, year: 2006, vol: 66, page: 4525, stat: Journal Article,

DRD2 genetic variation in relation to smoking and obesity in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Morton, Lindsay M; Wang, Sophia S; Bergen, Andrew W; Chatterjee, Nilanjan; Kvale, Paul; Welch, Robert; Yeager, Meredith; Hayes, Richard B; Chanock, Stephen J; Caporaso, Neil E
2006 Dec;16(12):901-910, Pharmacogenetics & Genomics
OBJECTIVES: Cigarette smoking is the leading cause of morbidity and mortality worldwide. We investigated the association between smoking behavior and genetic variations in the D2 dopamine receptor (DRD2), which mediates nicotine dependence. To assess the specificity of genetic effects, we also investigated other reward-motivated characteristics (obesity, alcohol consumption). METHODS: Four single nucleotide polymorphisms in DRD2 were genotyped in 2374 participants selected randomly from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. Single nucleotide polymorphism and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals derived from conditional logistic regression models, adjusted for race/ethnicity. RESULTS: DRD2 polymorphisms were associated with the risk of remaining a current smoker and obesity. Current smokers were more likely than former smokers to possess the variant TaqIA allele (rsmusical sharp1800497) in a dose-dependent model (ORCT=1.2, ORTT=1.5, P for linear trend=0.007). The DRD2 haplotype T-C-T-A [TaqIA(C/T)-957(T/C)-IVS6-83(G/T)- -50977(A/G)] was more common among current than former smokers (OR=1.3, P=0.006), particularly among heavy smokers (21+ cigarettes per day; OR=1.6, P=0.006), and was more common among obese than normal weight individuals (OR=1.4, P=0.02). CONCLUSIONS: Genetic variation in DRD2 is a modifier of the reward-motivated characteristics, smoking and obesity. As fewer than 15% of smokers who attempt to quit are able to maintain abstinence for greater than 3 months, our results support that DRD2 is an appropriate molecular target for smoking cessation treatments. Our results further support evaluation of DRD2 antagonists for obesity therapies
— id: 91651, year: 2006, vol: 16, page: 901, stat: Journal Article,

Cigarette smoking, N-acetyltransferase genes and the risk of advanced colorectal adenoma
Moslehi, Roxana; Chatterjee, Nilanjan; Church, Timothy R; Chen, Jinbo; Yeager, Meredith; Weissfeld, Joel; Hein, David W; Hayes, Richard B
2006 Sep;7(6):819-829, Pharmacogenomics
BACKGROUND: Cigarette use is associated with greater risk for colorectal adenoma, a colorectal cancer precursor. N-acetyltransferases, NAT1 and NAT2, are important enzymes involved in the metabolism of aromatic amine carcinogens present in cigarette smoke. Our interest is in the polymorphisms within the NAT1 and NAT2 genes that influence the tobacco-colorectal tumor relationship by impacting on the metabolic activation and detoxification of tobacco smoke-derived carcinogens. METHODS: In the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, we compared NAT1 and NAT2 gene variant distributions for 772 cases with left-sided advanced adenoma and 777 gender and age-matched controls. Individual NAT1 and NAT2 diplotypes were assigned and NAT2 acetylator phenotypes were derived. RESULTS: Risks for advanced colorectal adenoma were significantly increased among recent smokers (current smokers or those who quit less than 10 years ago) (odds ratio [OR] = 2.3, 95% confidence interval [CI]: 1.7-3.1) and among those who smoked more than 20 cigarettes per day (OR = 1.7, 95% CI: 1.3-2.2), compared with nonsmokers. Risk decreased with increasing NAT2 phenotypic activity (0: slow, 1: intermediate, and 2: rapid) (OR trend: 0.8; 95% CI: 0.7-1.0, p-trend = 0.04) overall. When stratified by smoking status, significant phenotype-associated trends were observed among recent smokers (OR trend = 0.4, 95% CI: 0.3-0.7, p trend <0.001) (p-interaction = 0.02), but not among past or nonsmokers. Diplotypes most strongly associated with lower risks in smokers were NAT2*4/*5B (OR = 0.3, 95% CI: 0.1-0.8, p = 0.01) and NAT2*4/*4 (OR = 0.2, 95% CI: 0.04-0.7, p = 0.02), categorized as intermediate and rapid acetylators, respectively. One NAT1 diplotype, NAT1*4/*10 (OR = 0.5, 95% CI: 0.3-0.9, p = 0.03), was also associated with a decreased risk in smokers. CONCLUSIONS: Our study indicated that NAT2 gene variants associated with a slow acetylator phenotype were more susceptible to the effects of tobacco smoking with respect to adenoma risk, providing leads for disease prevention
— id: 91646, year: 2006, vol: 7, page: 819, stat: Journal Article,

High serum selenium and reduced risk of advanced colorectal adenoma in a colorectal cancer early detection program
Peters, Ulrike; Chatterjee, Nilanjan; Church, Timothy R; Mayo, Charlotte; Sturup, Stefan; Foster, Charles B; Schatzkin, Arthur; Hayes, Richard B
2006 Feb;15(2):315-320, Cancer epidemiology biomarkers & prevention
BACKGROUND: Epidemiologic and animal studies suggest that selenium may reduce risk of colorectal cancer. However, the epidemiologic data is mainly from relatively small investigations, limiting their interpretation. Although substantial evidence suggests that smoking is a strong effect modifier for other antioxidative nutrients, little is known about smoking-selenium interactions in colorectal tumors. METHODS: We studied the association of serum selenium and advanced colorectal adenoma, a cancer precursor, in 758 cases and 767 sex- and race-matched controls, randomly selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma (> or = 1 cm or villous elements, or high-grade dysplasia) of the distal colon, and controls had a negative sigmoidoscopy. RESULTS: The multivariable odds ratio (OR) comparing participants in the highest quintile of serum selenium with those in the lowest quintile was 0.76 [95% confidence interval (95% CI), 0.53-1.10; P(trend) = 0.01]. The inverse association between serum selenium and advanced colorectal adenoma was significant among recent smokers (OR, 0.53; 95% CI, 0.27-1.01 for highest versus lowest tertile; P(trend) = 0.008). Serum selenium was unrelated to adenoma risk in nonsmokers and former smokers who quit smoking > or = 10 years ago. CONCLUSION: Selenium may reduce the risk of developing advanced colorectal adenoma, particularly among the high-risk group of recent smokers
— id: 91637, year: 2006, vol: 15, page: 315, stat: Journal Article,

Occupational exposures and head and neck cancers among Swedish construction workers
Purdue, Mark P; Jarvholm, Bengt; Bergdahl, Ingvar A; Hayes, Richard B; Baris, Dalsu
2006 Aug;32(4):270-275, Scandinavian journal of work environment & health
OBJECTIVES: Occupational exposures in the construction industry may increase the risk of head and neck cancers, although the epidemiologic evidence is limited by problems of low study power and inadequate adjustment for tobacco use. In an attempt to address this issue, the relationship between selected occupational exposures and head and neck cancer risk was investigated using data from a large cohort of Swedish construction workers. METHODS: Altogether 510 squamous cell carcinomas of the head and neck (171 in the oral cavity, 112 in the pharynx, 227 in the larynx) were identified during 1971-2001 among 307 799 male workers in the Swedish construction industry. Exposure to diesel exhaust, asbestos, organic solvents, metal dust, asphalt, wood dust, stone dust, mineral wool, and cement dust was assessed using a semi-quantitative job-exposure matrix. Rate ratios (RR) and 95% confidence intervals (95% CI) were calculated for head and neck cancers in relation to occupational exposure, using Poisson regression with adjustment for age and smoking status. RESULTS: Asbestos exposure was related to an increased laryngeal cancer incidence (RR 1.9, 95% CI 1.2-3.1). Excesses of pharyngeal cancer were observed among workers exposed to cement dust (RR 1.9, 95% CI 1.2-3.1). No occupational exposures were associated with oral cavity cancer. These findings did not materially change upon additional adjustment for cigarette pack-years. CONCLUSIONS: These findings offer further evidence that asbestos increases the risk of laryngeal cancer. The observation of a positive association between cement dust exposure and pharyngeal cancer warrants further investigation
— id: 91645, year: 2006, vol: 32, page: 270, stat: Journal Article,

Effect of homeodomain protein NKX3.1 R52C polymorphism on prostate gland size
Rodriguez Ortner, Elizabeth; Hayes, Richard B; Weissfeld, Joel; Gelmann, Edward P
2006 Feb;67(2):311-315, Urology
OBJECTIVES: To determine the association between prostatic enlargement and a cytosine for thymine genetic polymorphism at nucleotide 154 (C154T) of the NKX3.1 prostate homeobox gene. The polymorphism, found in 10% of the population, affects the NKX3.l protein by replacing a cysteine for arginine at amino acid 52 and alters protein phosphorylation and DNA binding. METHODS: A study group of men without prostate cancer from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial was identified who had had at least three annual serial digital rectal examinations by a single examiner. The cohort of 772 men consisted of the lowest and highest tertiles of the entire study group as defined by two-dimensional measurements at digital rectal examination. The TaqMan allelic discrimination assay was used to genotype NKX3.1 for the nucleotide 154 polymorphism. RESULTS: The men in the lower tertile (n = 413) had a mean age of 60.8 years, mean prostate-specific antigen level of 1.2 ng/mL, and mean prostate volume of 37.9 +/- 4.5 cm3. The men in the upper tertile (n = 359) had a mean age of 61.6 years, mean prostate-specific antigen level of 2.1 ng/mL, and mean prostate volume of 61 +/- 6.3 cm3. The men in the upper tertile had a greater likelihood of having a clinical history of benign prostatic hyperplasia and more frequent nocturia. The presence of one or two polymorphic NKX3.1 alleles conferred a risk of 1.6 (95% confidence interval 1.0 to 2.6) for an enlarged prostate (highest tertile). CONCLUSIONS: The NKX3.1 nucleotide 154 C/T or T/T genotype increases the relative odds for prostatic enlargement. The group with prostatic enlargement also had increased clinical benign prostatic hyperplasia and nocturia
— id: 91633, year: 2006, vol: 67, page: 311, stat: Journal Article,

Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity
Shen, Min; Lan, Qing; Zhang, Luoping; Chanock, Stephen; Li, Guilan; Vermeulen, Roel; Rappaport, Stephen M; Guo, Weihong; Hayes, Richard B; Linet, Martha; Yin, Songnian; Yeager, Meredith; Welch, Robert; Forrest, Matthew S; Rothman, Nathaniel; Smith, Martyn T
2006 Oct;27(10):2083-2089, Carcinogenesis
Benzene is a recognized hematotoxicant and carcinogen that produces genotoxic damage. DNA double-strand breaks (DSB) are one of the most severe DNA lesions caused directly and indirectly by benzene metabolites. DSB may lead to chromosome aberrations, apoptosis and hematopoietic progenitor cell suppression. We hypothesized that genetic polymorphisms in genes involved in DNA DSB repair may modify benzene-induced hematotoxicity. We analyzed one or more single nucleotide polymorphisms (SNPs) in each of seven candidate genes (WRN, TP53, NBS1, BRCA1, BRCA2, XRCC3 and XRCC4) in a study of 250 workers exposed to benzene and 140 controls in China. Four SNPs in WRN (Ex4 -16 G > A, Ex6 +9 C > T, Ex20 -88 G > T and Ex26 -12 T > G), one SNP in TP53 (Ex4 +119 C > G) and one SNP in BRCA2 (Ex11 +1487 A > G) were associated with a statistically significant decrease in total white blood cell (WBC) counts among exposed workers. The SNPs in WRN and TP53 remained significant after accounting for multiple comparisons. One or more SNPs in WRN had broad effects on WBC subtypes, with significantly decreased granulocyte, total lymphocyte, CD4(+)-T cell, CD8(+)-T cell and monocyte counts. Haplotypes of WRN were associated with decreased WBC counts among benzene-exposed subjects. Likewise, subjects with TP53 Ex4 +119 C > G variant had reduced granulocyte, CD4(+)-T cell and B cell counts. The effect of BRCA2 Ex11 +1487 A > G polymorphism was limited to granulocytes. These results suggest that genetic polymorphisms in WRN, TP53 and BRCA2 that maintain genomic stability impact benzene-induced hematotoxicity
— id: 91640, year: 2006, vol: 27, page: 2083, stat: Journal Article,

A prospective study of meat and meat mutagens and prostate cancer risk
Cross, Amanda J; Peters, Ulrike; Kirsh, Victoria A; Andriole, Gerald L; Reding, Douglas; Hayes, Richard B; Sinha, Rashmi
2005 Dec 15;65(24):11779-11784, Cancer research
High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of > or =7). Total, red, or white meat intake was not associated with prostate cancer risk. More than 10 g/d of very well done meat, compared with no consumption, was associated with a 1.4-fold increased risk of prostate cancer [95% confidence interval (95% CI), 1.05-1.92] and a 1.7-fold increased risk (95% CI, 1.19-2.40) of incident disease. Although there was no association with MeIQx and DiMeIQx, the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer (95% CI, 1.01-1.48) and a 1.3-fold increased risk of incident disease (95% CI, 1.01-1.61). In conclusion, very well done meat was positively associated with prostate cancer risk. In addition, this study lends epidemiologic support to the animal studies, which have implicated PhIP as a prostate carcinogen
— id: 91630, year: 2005, vol: 65, page: 11779, stat: Journal Article,

DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients
Gal, Thomas J; Huang, Wen-Yi; Chen, Chu; Hayes, Richard B; Schwartz, Stephen M
2005 Dec;115(12):2221-2231, Laryngoscope
OBJECTIVES/HYPOTHESIS: We tested the hypothesis that polymorphisms in genes involved in DNA repair pathways are associated with the development of second primary neoplasms of the upper aerodigestive tract (UADT), as well as mortality, in patients previously diagnosed with oral squamous cell cancer (OSCC). METHODS: DNA specimens from 279 OSCC patients who had participated in two previous population-based case-control studies were assayed for the following polymorphisms: X-ray repair cross-complementing (XRCC) 1 Arg399Gln, XRCC3 Thr241Met, xeroderma pigmentosum complementing group D (XPD) Lys751Gln, and O-methylguanine- DNA methyltransferase (MGMT) Leu84Phe and Val143Ile. Baseline demographic information was obtained from personal interviews and tumor characteristics and treatment were obtained from cancer registry files. Cox proportional hazards models were used to calculate hazards ratio (HR) estimates for each polymorphism in relation to the risk of developing second primary neoplasms at any site, UADT, and head and neck. HRs were also determined for associations with all-cause mortality and oral cancer specific mortality. RESULTS: A significant increased risk of second neoplasms (all sites combined, as well as for UADT sites and for head and neck squamous cell cancers) was observed among XRCC3 241Met allele homozygotes (HR 2.65-3.44, P < .02). No significant association with the development of second neoplasms was observed for the XRCC1 399Gln, XPD 751Gln, or MGMT 84Phe or 143Ile alleles. Although no associations with oral cancer-specific mortality were observed, we found a significant inverse association between all-cause mortality and possessing at least one copy of the XRCC1 399Gln allele (HR 0.68, 95% confidence interval [CI] 0.47-0.97, P = .03), as well as a suggestion of a direct association between all-cause mortality and having one copy of the XRCC3 241Met allele (HR 1.39, 95% CI 0.95-2.03, P = .09). CONCLUSIONS: Polymorphisms in the DNA repair enzyme gene XRCC3 241Met was associated with an increased risk of second neoplasms, and polymorphisms of the XRCC1 399Gln gene were associated with a decreased risk of all-cause mortality in patients with primary OSCC. These findings require confirmation in other populations before the clinical implications can be considered
— id: 91631, year: 2005, vol: 115, page: 2221, stat: Journal Article,

Molecular epidemiology: convergence between toxicology and epidemiology
Hayes, Richard B; Husgafvel-Pursiainen, Kirsti; Vainio, Harri
2005 Dec 30;592(1-2):1-2, Mutation research
— id: 91616, year: 2005, vol: 592, page: 1, stat: Journal Article,

Methods for etiologic and early marker investigations in the PLCO trial
Hayes, Richard B; Sigurdson, Alice; Moore, Lee; Peters, Ulrike; Huang, Wen-Yi; Pinsky, Paul; Reding, Douglas; Gelmann, Edward P; Rothman, Nat; Pfeiffer, Ruth M; Hoover, Robert N; Berg, Christine D
2005 Dec 30;592(1-2):147-154, Mutation research
With the rapid development of biomarkers and new technologies, large-scale biologically-based cohort studies present expanding opportunities for population-based research on disease etiology and early detection markers. The prostate, lung, colorectal and ovarian cancer (PLCO) screening trial is a large randomized trial designed to determine if screening for these cancers leads to mortality reduction for these diseases. Within the Trial, the PLCO etiology and early marker study (EEMS) identifies risk factors for cancer and other diseases and evaluates biologic markers for the early detection of disease. EEMS includes 155,000 volunteers who provide basic risk factor information. Serial blood samples are collected at each of six screening rounds (including one collection for cryopreserved whole blood) from screening arm participants (77,000 subjects) and buccal cells are collected from those in the control arm of the trial. Etiologic studies consider environmental (e.g., diet), biochemical, and genetic factors. Early detection studies focus on blood-based biologic markers of early disease. Clinical epidemiology is also an important component of the PLCO trial
— id: 91622, year: 2005, vol: 592, page: 147, stat: Journal Article,

CYP1A1 Val462 and NQO1 Ser187 polymorphisms, cigarette use, and risk for colorectal adenoma
Hou, Lifang; Chatterjee, Nilanjan; Huang, Wen-Yi; Baccarelli, Andrea; Yadavalli, Sunita; Yeager, Meredith; Bresalier, Robert S; Chanock, Stephen J; Caporaso, Neil E; Ji, Bu-Tian; Weissfeld, Joel L; Hayes, Richard B
2005 Jun;26(6):1122-1128, Carcinogenesis
Cigarette use is a risk factor for colorectal adenoma, a known precursor of colorectal cancer. Polymorphic variants in NQO1 and CYP1A1 influence the activation of carcinogenic substances in tobacco smoke, possibly impacting on tobacco-associated risks for colorectal tumors. We investigated the association of cigarette smoking with risk for advanced colorectal adenoma in relation to the CYP1A1 Val(462) and NQO1 Ser(187) polymorphic variants. Subjects were 725 non-Hispanic Caucasian cases with advanced colorectal adenoma of the distal colon (descending colon, sigmoid and rectum) and 729 gender- and ethnicity-matched controls, randomly selected from participants in the prostate, lung, colorectal and ovarian cancer screening trial. Subjects carrying either CYP1A1 Val(462) or NQO1 Ser(187) alleles were weakly associated with risk of colorectal adenoma; however, subjects carrying both CYP1A1 Val(462) and NQO1 Ser(187) alleles showed increased risks (OR = 2.2, 95% CI = 1.1-4.5), particularly among recent (including current) (OR = 17.4, 95% CI = 3.8-79.8, P for interaction = 0.02) and heavy cigarette smokers (>20 cigarettes/day) (OR = 21.1, 95% CI = 3.9-114.4, P for interaction = 0.03) compared with non-smokers who did not carry either of these variants. These genotypes were unassociated with risk in non-smokers. In analysis of adenoma subtypes, the combined gene variants were most strongly associated with the presence of multiple adenoma (P = 0.002). In summary, joint carriage of CYP1A1 Val(462) and NQO1 Ser(187) alleles, particularly in smokers, was related to colorectal adenoma risk, with a propensity for formation of multiple lesions
— id: 91606, year: 2005, vol: 26, page: 1122, stat: Journal Article,

Microsomal epoxide hydrolase polymorphisms and risk for advanced colorectal adenoma
Huang, Wen-Yi; Chatterjee, Nilanjan; Chanock, Stephen; Dean, Michael; Yeager, Meredith; Schoen, Robert E; Hou, Li-Fang; Berndt, Sonja I; Yadavalli, Sunita; Johnson, Christine C; Hayes, Richard B
2005 Jan;14(1):152-157, Cancer epidemiology biomarkers & prevention
Cigarette smoking is a risk factor for colorectal adenoma, a precursor of colorectal cancer. Microsomal epoxide hydrolase (EPHX1) metabolizes polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Nonsynonymous variants of EPHX1 at Tyr(113)His (exon 3) and His(139)Arg (exon 4) are associated, respectively, with low ((113)His) and high ((139)Arg) predicted activity. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we evaluated risks for advanced adenoma in relation to cigarette use and these two EPHX1 variants. We compared 772 cases with advanced adenoma (adenoma >/=1 cm or containing high-grade dysplasia or villous, including tubulovillous, elements) of the distal colon (left-sided, descending colon and sigmoid or rectum) to 777 gender- and age-matched controls who were screen-negative for left-sided adenoma. Compared to those with homozygous genotypes predicting low EPHX1 activity, advanced adenoma risks tended to be elevated for carriers of (113)TyrTyr [odds ratios (OR), 1.5; 95% confidence intervals (CI), 1.0-2.2] and (139)ArgArg (OR, 1.4; 95% CI, 0.8-2.5) and for subjects who carried a greater number of the alleles ((113)Tyr or (139)Arg) associated with high predicted enzymatic activity (P(trend) = 0.03). The increased risk associated with the increasing number of putative high-activity alleles was most apparent among current and recent (quit <10 years) cigarette smokers (P(trend) = 0.02). In conclusion, EPHX1 variants at codon 113 and 139 associated with high predicted enzymatic activity appear to increase risk for colorectal adenoma, particularly among recent and current smokers
— id: 91601, year: 2005, vol: 14, page: 152, stat: Journal Article,

Selected DNA repair polymorphisms and gastric cancer in Poland
Huang, Wen-Yi; Chow, Wong-Ho; Rothman, Nat; Lissowska, Jolanta; Llaca, Victor; Yeager, Meredith; Zatonski, Witold; Hayes, Richard B
2005 Aug;26(8):1354-1359, Carcinogenesis
Impaired DNA repair capacity may adversely affect cancer risk, particularly in subjects exposed to DNA damaging carcinogens, as found in tobacco smoke, or among subjects deficient for protective factors, as found in fruits and vegetables. We studied tobacco use, fruit and vegetable intake, and common non-synonymous single nucleotide polymorphisms in four DNA repair genes in relation to gastric cancer risk, in a population-based, case-control study of 281 incident gastric cancer cases and 390 controls, in Warsaw, Poland. Multivariate logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Increased risks of gastric cancer were found for smokers (OR=3.1, CI=1.9-5.1 for pack-years>or=40 versus never smokers) and subjects with low fruit intake (OR=2.2, CI=1.3-3.6 for 1st versus 4th quartile); risk associated with vegetable intake was not statistically significant. Allele frequencies among the controls were consistent with those previously reported for the 5 polymorphisms studied: XRCC1-Arg399Gln, XPD-Lys751Gln, MGMT-Ile143Val, Leu84Phe, and XRCC3-Thr241Met. None of the studied polymorphisms were independently associated with gastric cancer risk. Smoking-associated risks, however, were greatest for carriers of the XRCC1-399 ArgArg genotype (Pinteraction=0.004). Risks associated with low intake of fruits or vegetables tended to be modified by selected polymorphisms in XRCC1, XPD and MGMT (Pinteraction=0.1-0.2). Risk modification was not found for the other repair polymorphisms. Selected DNA repair polymorphisms did not have independent effects on gastric cancer risk; however, they may modify smoking- and probably diet-related risks for this disease. These results need replication in larger epidemiological studies of gastric cancer
— id: 91608, year: 2005, vol: 26, page: 1354, stat: Journal Article,

Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer: a pooled analysis
Huang, Wen-Yi; Olshan, Andrew F; Schwartz, Stephen M; Berndt, Sonja I; Chen, Chu; Llaca, Victor; Chanock, Stephen J; Fraumeni, Joseph F Jr; Hayes, Richard B
2005 Jul;14(7):1747-1753, Cancer epidemiology biomarkers & prevention
Tobacco and alcohol consumption are the major risk factors for head and neck cancer, likely due to DNA-damaging processes. Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. Pooling data and DNA specimens from three case-control studies in western Washington State, North Carolina, and Puerto Rico, totaling 555 cases (430 whites) and 792 controls (695 whites), we studied the risk of head and neck cancer in relation to common nonsynonymous single-nucleotide polymorphisms in four DNA repair genes: MGMT (Leu84Phe and Ile143Val), XRCC1 (Arg399Gln), XPD (Lys751Gln), and XRCC3 (Thr241Met). All single-nucleotide polymorphisms were assayed in a single laboratory. Among whites, carriage of the MGMT Phe84 [odds ratio (OR), 0.71; 95% confidence interval (95% CI), 0.51-0.98] or Val143 (OR, 0.66; 95% CI, 0.47-0.92) allele was associated with a decreased risk of head and neck cancer; the haplotype distribution for MGMT differed significantly between cases and controls (covariate-adjusted global permutation test, P = 0.012). The XRCC1 GlnGln399 genotype was also associated with decreased risk among whites (OR, 0.56; 95% CI, 0.32-0.94), whereas XPD751 and XRCC3241 were not associated with risk. Alcohol-related risks tended to vary with DNA repair genotypes, especially for MGMT variants, whereas no effect modification was noted with tobacco use. Consistent findings from three case-control studies suggest that selected DNA repair enzymes may play a role in head and neck carcinogenesis
— id: 91620, year: 2005, vol: 14, page: 1747, stat: Journal Article,

Microsatellite polymorphisms in the epidermal growth factor receptor (EGFR) gene and the transforming growth factor-alpha (TGFA) gene and risk of oral cancer in Puerto Rico
Kang, Daehee; Gridley, Gloria; Huang, Wen-Yi; Engel, Lawrence S; Winn, Deborah M; Brown, Linda M; Bravo-Otero, Eleuterio; Wu, Tianxia; Diehl, Scott R; Hayes, Richard B
2005 May;15(5):343-347, Pharmacogenetics & Genomics
OBJECTIVES AND METHODS: Risks of oral cancer related to a CA microsatellite repeat polymorphism in intron 1 of the epidermal growth factor receptor (EGFR) gene and a TaqI polymorphism in the transforming growth factor-alpha (TGFA) gene were evaluated in a population-based case-control study consisting of 157 cases and 149 controls recruited in Puerto Rico. RESULTS: Carriers of > or = 16 CA repeats in EGFR showed a 1.9-fold increased risk for oral cancer (OR=1.9, 95% CI=1.0-3.5). Risks also tended to increase with decreasing number of alleles with > or = 16 CA repeats (P for trend=0.06). Our data suggested a non-significant reduction in risk for subjects heterozygous for the TGFA polymorphism (OR=0.6, 95% CI=0.2-1.3). CONCLUSIONS: The EGFR-associated risk appeared to be independent of tobacco and alcohol use and may be restricted primarily to subjects who consumed low amounts of fresh fruits and vegetables (OR=5.9, 95%CI: 2.3-15.2). These data implicate dietary and molecular targets for oral cancer prevention
— id: 91612, year: 2005, vol: 15, page: 343, stat: Journal Article,

Variation of long-lived free radicals responsible for the EPR native signal in bone of aged or diseased human females and ovariectomized adult rats
Kenner, G H; Brik, A B; Liu, G; Haskell, E H; Hayes, R B; Knight, J A; Vajda, E G; Miller, S C; Jee, W S S; Barrus, J K
2005 Jun;39(3):255-262, Radiation measurements
The purpose of this study was to gain insights into the variations seen in the electron paramagnetic resonance (EPR) spectroscopy of the native signals of teeth and bones used for retrospective dosimetry measurements. We determined that changes occur in the long-lived free radicals responsible for the native signal of cortical bone in aging or diseased human females and aged ovariectomized rats. This was done by measuring the magnitude of the broad (BC) and narrow (NC) components of the native EPR signal of bone following chemical extraction, aging, crushing and thermal annealing. Bone from the upper midshaft of femora of young (17-34 years old, n=5) and elderly (70-92 years old, n=18) females was examined. The results showed that the elderly women had significantly higher BC than the younger women (P<0.01). A similar interpretation was made of the data from an aging female rat osteoporosis model. The results for the NC signals were similar. Finally, dramatic decreases in both NC and BC signals were seen in HIV positive and uncontrolled diabetic (one each) patients indicating the need for studying this signal for a broad spectrum of metabolic disorders. Experiments were performed which strongly indicate that iron liganded with organic molecules is the source of the BC signal. Finally, the accuracy achieved in this study indicates that resolving the dosimetric signal (g=2.0018) should be improved by subtraction of the deconvoluted NC and BC signals from the original spectrum
— id: 91613, year: 2005, vol: 39, page: 255, stat: Journal Article,

Genetic variation in the HSD17B1 gene and risk of prostate cancer
Kraft, Peter; Pharoah, Paul; Chanock, Stephen J; Albanes, Demetrius; Kolonel, Laurence N; Hayes, Richard B; Altshuler, David; Andriole, Gerald; Berg, Christine; Boeing, Heiner; Burtt, Noel P; Bueno-de-Mesquita, Bas; Calle, Eugenia E; Cann, Howard; Canzian, Federico; Chen, Yen-Ching; Crawford, David E; Dunning, Alison M; Feigelson, Heather S; Freedman, Matthew L; Gaziano, John M; Giovannucci, Ed; Gonzalez, Carlos Alberto; Haiman, Christopher A; Hallmans, Goran; Henderson, Brian E; Hirschhorn, Joel N; Hunter, David J; Kaaks, Rudolf; Key, Timothy; Le Marchand, Loic; Ma, Jing; Overvad, Kim; Palli, Domenico; Pike, Malcolm C; Riboli, Elio; Rodriguez, Carmen; Setiawan, Wendy V; Stampfer, Meir J; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Travis, Ruth; Trichopoulou, Antonia; Virtamo, Jarmo; Wacholder, Sholom
2005 Nov;1(5):e68-e68, PLoS Genetics
Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites
— id: 91629, year: 2005, vol: 1, page: e68, stat: Journal Article,

Polymorphisms in cytokine and cellular adhesion molecule genes and susceptibility to hematotoxicity among workers exposed to benzene
Lan, Qing; Zhang, Luoping; Shen, Min; Smith, Martyn T; Li, Guilan; Vermeulen, Roel; Rappaport, Stephen M; Forrest, Matthew S; Hayes, Richard B; Linet, Martha; Dosemeci, Mustafa; Alter, Blanche P; Weinberg, Rona S; Yin, Songnian; Yeager, Meredith; Welch, Robert; Waidyanatha, Suramya; Kim, Sungkyoon; Chanock, Stephen; Rothman, Nathaniel
2005 Oct 15;65(20):9574-9581, Cancer research
Benzene is a recognized hematotoxin and leukemogen but its mechanism of action and the role of genetic susceptibility are still unclear. Cytokines, chemokines, and cellular adhesion molecules are soluble proteins that play an important regulatory role in hematopoiesis. We therefore hypothesized that variation in these genes could influence benzene-induced hematotoxicity. We analyzed common, well-studied single-nucleotide polymorphisms (SNPs) in 20 candidate genes drawn from these pathways in a study of 250 workers exposed to benzene and 140 unexposed controls in China. After accounting for multiple comparisons, SNPs in five genes were associated with a statistically significant decrease in total WBC counts among exposed workers [IL-1A (-889C>T), IL-4 (-1098T>G), IL-10 (-819T>C), IL-12A (8685G>A), and VCAM1 (-1591T>C)], and one SNP [CSF3 (Ex4-165C>T)] was associated with an increase in WBC counts. The adhesion molecule VCAM1 variant was particularly noteworthy as it was associated with a decrease in B cells, natural killer cells, CD4+ T cells, and monocytes. Further, VCAM1 (-1591T>C) and CSF3 (Ex4-165C>T) were associated, respectively, with decreased (P = 0.041) and increased (P = 0.076) CFU-GEMM progenitor cell colony formation in 29 benzene-exposed workers. This is the first report to provide evidence that SNPs in genes that regulate hematopoiesis influence benzene-induced hematotoxicity
— id: 91627, year: 2005, vol: 65, page: 9574, stat: Journal Article,

Hemochromatosis gene mutations and distal adenomatous colorectal polyps
McGlynn, Katherine A; Sakoda, Lori C; Hu, Ying; Schoen, Robert E; Bresalier, Robert S; Yeager, Meredith; Chanock, Stephen; Hayes, Richard B; Buetow, Kenneth H
2005 Jan;14(1):158-163, Cancer epidemiology biomarkers & prevention
Iron has been suggested to be a risk factor for colorectal neoplasia. Some individuals who are heterozygous for mutations in the hemochromatosis gene (HFE) have higher than average serologic measures of iron. We therefore investigated whether heterozygosity for HFE mutations was related to risk of advanced distal adenoma and whether the relationship was affected by dietary iron intake. In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 679 persons with advanced distal adenoma and 697 control persons were genotyped for the two major HFE mutations (C282Y and H63D), one HFE polymorphism (IVS2+4), and one polymorphism (G142S) in the transferrin receptor gene (TFRC). HFE haplotypes were also created to examine the effect of haplotype on risk. Food frequency questionnaire data were used to estimate daily iron intake. There was no relationship between any HFE genotype or haplotype and advanced adenoma. Stratification of HFE genotype by TFRC genotype did not change the results. In addition, there was no relationship between dietary iron intake and risk of adenoma or between HFE genotype and risk of adenoma, stratified by iron intake. These results do not support a relationship between HFE heterozygosity and risk of advanced distal adenoma
— id: 91602, year: 2005, vol: 14, page: 158, stat: Journal Article,

GSTM1, GSTT1, and GSTP1 polymorphisms and risk of advanced colorectal adenoma
Moore, Lee E; Huang, Wen-Yi; Chatterjee, Nilanjan; Gunter, Marc; Chanock, Stephen; Yeager, Meredith; Welch, Bob; Pinsky, Paul; Weissfeld, Joel; Hayes, Richard B
2005 Jul;14(7):1823-1827, Cancer epidemiology biomarkers & prevention
Cigarette smoking is a risk factor for colon adenoma. The glutathione S-transferase enzymes are involved in the detoxification of carcinogenic compounds including those found in tobacco smoke, and thus, may be important modifiers of individual risk of developing this disease. We examined the prevalence of GSTM1 and GSTT1 gene deletions, and two GSTP1 polymorphisms in 772 cases with advanced colorectal adenomas (>1 cm, villous elements or high-grade dysplasia) of the distal colon (descending or sigmoid colon or rectum) and 777 sigmoidoscopy negative controls enrolled in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Epidemiologic data on smoking was collected by self-administered questionnaire and DNA was extracted from whole blood or buffy coat. For GSTM1 and GSTT1, we used a newly developed TaqMan-based assay capable of discriminating heterozygous (+/-) individuals from those with two active alleles (+/+) and homozygous deletions (-/-). For GSTP1, the I105V and the A114V substitutions were identified using end point 5' nuclease assays (TaqMan). Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were determined using unconditional logistic regression, controlling for age, race, and gender. Advanced adenoma risk was increased in current/former smokers (OR, 1.4; 95% CI, 1.2-1.8). Risks were decreased in subjects with > or =1 inactive GSTM1 alleles (OR, 0.6; 95% CI, 0.4-0.9); and the association was independent of smoking status (P interaction = 0.59). Having > or =1 inactive GSTT1 allele was associated with increased risk among smokers (OR, 1.4; 95% CI, 1.1-1.9; P trend = 0.02) but not among never smokers (OR, 0.9; 95% CI, 0.6-1.3) and a significant interaction between smoking and genotype was observed (P interaction = 0.05). In summary, this is the first study to report associations between colorectal adenomas and GSTM1 wild-type and GSTT1 null allele among smokers. These findings only became apparent using a newly developed assay able to distinguish heterozygous from wild-type individuals. Our data provide evidence that phenotypic differences between these two groups exist
— id: 91621, year: 2005, vol: 14, page: 1823, stat: Journal Article,

Prostate biopsy following a positive screen in the prostate, lung, colorectal and ovarian cancer screening trial
Pinsky, Paul F; Andriole, Gerald L; Kramer, Barnett S; Hayes, Richard B; Prorok, Philip C; Gohagan, John K
2005 Mar;173(3):746-750, Journal of urology
PURPOSE: The benefit of prostate specific antigen (PSA) and digital rectal examination (DRE) screening for prostate cancer is under evaluation in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Followup of positive screens in PLCO is done by subject personal physicians and it is outside of trial control. We describe the pattern of prostate biopsy in men with positive screens in PLCO. MATERIALS AND METHODS: We examined all men with positive baseline PSA or DRE screens and men with positive post-baseline screens occurring by December 2000. RESULTS: Of 2,717 men with positive PSA (greater than 4 ng/ml) at baseline 41% and 64% underwent biopsy within 1 and 3 years, respectively. A screening PSA of 7 to 10 and greater than 10 ng/ml at baseline was associated with significantly higher biopsy rates (HR 1.9 and 2.6, respectively) compared to PSA 4 to 7 ng/ml. The 1,793 in men whom the first positive PSA was after baseline had a lower overall biopsy rate (50% within 3 years). Furthermore, PSA above 7 ng/ml were not associated with higher biopsy rates in this group. The 4,449 men with positive DRE screens and negative PSA had a 3-year biopsy rate of 27%. Men with positive DRE at diagnostic followup had a biopsy rate of around 90%. However, few men, even of those with positive DRE screens, had positive diagnostic DREs. CONCLUSIONS:: These biopsy rates following positive PSA and DRE screens are likely to be representative of national rates. These results suggest that PLCO is evaluating the effects of screening in a contemporary and robust manner
— id: 91605, year: 2005, vol: 173, page: 746, stat: Journal Article,

Variability in flexible sigmoidoscopy performance among examiners in a screening trial
Pinsky, Paul F; Schoen, Robert E; Weissfeld, Joel L; Kramer, Barnett; Hayes, Richard B; Yokochi, Lance
2005 Aug;3(8):792-797, Clinical Gastroenterology & Hepatology
BACKGROUND & AIMS: The efficacy of flexible sigmoidoscopy (FSG) in reducing colorectal cancer mortality is being evaluated in randomized trials. In 2 European trials, wide variability across examiners in FSG performance was noted. We report on the performance of examiners in the US randomized trial: the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. METHODS: Screening was performed at 10 geographically dispersed clinical centers. Patients with screens positive for a lesion or mass were referred to their private health care providers for endoscopic follow-up evaluation; lesions were not removed and a biopsy examination was not performed at screening. FSG performance among 64 examiners at these centers, each performing 100 or more baseline FSG examinations, with an aggregate of almost 50,000 examinations, was analyzed. RESULTS: Screen-positivity results among examiners ranged from 9%-58%, with a coefficient of variation (CV) of 36%. CVs were 29% for distal polyp detection and 21% for distal adenoma detection. Inadequate rates ranged from 1%-27% (CV, 52%). Examiners with higher screen-positivity rates had higher false-positive rates, defined as a positive screen with no distal lesion found on endoscopic follow-up evaluation. CONCLUSIONS: Considerable variability exists in the rates of positive screens and in polyp and adenoma detection rates among FSG examiners performing the procedures using a common protocol
— id: 91628, year: 2005, vol: 3, page: 792, stat: Journal Article,

Hormone replacement therapy, reproductive history, and colorectal adenomas: data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (United States)
Purdue, Mark P; Mink, Pamela J; Hartge, Patricia; Huang, Wen-Yi; Buys, Saundra; Hayes, Richard B
2005 Oct;16(8):965-973, Cancer causes & control. ccc
OBJECTIVE: Findings from some epidemiologic studies of colorectal cancer and adenoma suggest that the protective effect of post-menopausal hormone replacement therapy (HRT) may differ across categories of age and body mass index (BMI). We conducted an analysis of women participating in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to investigate the relationship between HRT use and prevalent adenoma, both overall and across different population subgroups. METHODS: Women aged 55-74 were randomized to screening by flexible sigmoidoscopy at ten PLCO screening centers between September 1993 and September 2001. We identified 1468 women with at least one left-sided adenoma and 19,203 without adenoma or colorectal cancer. Information about HRT and reproductive factors was obtained from a self-administered questionnaire. RESULTS: Compared to never use of HRT, current use was associated with a decreased prevalence of left-sided adenoma (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.75-0.97). We found no evidence of dose-response with increasing duration of use for current or former users. The association with current HRT use was stronger among women aged 65+ (OR 0.69; 95% CI 0.56-0.84), with a BMI<30 (OR 0.82; 95% CI 0.71-0.95) and who regularly use aspirin or ibuprofen (OR 0.77; 95% CI 0.65-0.91). Other reproductive factors were not significantly associated with adenoma prevalence. CONCLUSIONS: Our findings suggest that current HRT use may protect against colorectal adenoma, and that this protective effect is short-lived following cessation of use
— id: 91624, year: 2005, vol: 16, page: 965, stat: Journal Article,

Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps
Schoen, Robert E; Weissfeld, Joel L; Kuller, Lewis H; Thaete, F Leland; Evans, Rhobert W; Hayes, Richard B; Rosen, Clifford J
2005 Aug;129(2):464-475, Gastroenterology
BACKGROUND & AIMS: Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apoptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer. METHODS: Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements. RESULTS: Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0-2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1-3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2-3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3-6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0-5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1-4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk. CONCLUSIONS: Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps
— id: 91623, year: 2005, vol: 129, page: 464, stat: Journal Article,

Meat, meat cooking methods and preservation, and risk for colorectal adenoma
Sinha, Rashmi; Peters, Ulrike; Cross, Amanda J; Kulldorff, Martin; Weissfeld, Joel L; Pinsky, Paul F; Rothman, Nathaniel; Hayes, Richard B
2005 Sep 1;65(17):8034-8041, Cancer research
Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo[4,5]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma
— id: 91625, year: 2005, vol: 65, page: 8034, stat: Journal Article,

Development and application of a simple routine method for the determination of selenium in serum by octopole reaction system ICPMS
Sturup, Stefan; Hayes, Richard B; Peters, Ulrike
2005 Feb;381(3):686-694, Analytical & bioanalytical chemistry
The aim of the study was to develop an inductively coupled plasma mass spectrometry (ICPMS) method for robust and simple routine determination of selenium in serum. Polyatomic interferences on 76Se, 77Se, and 78Se were removed by applying an octopole reaction system ICPMS with the reaction cell pressurized with H2 gas. We developed a novel simple optimization routine for the H2 gas flow based on a signal-to-noise ratio (SNR) calculation of the selenium signal measured in a single selenium standard. The optimum H2 flow was 2.9 mL min-1. The selenium content in serum was determined after a 50-fold dilution with 0.16 M HNO3 and quantified by using addition calibration and gallium as an internal standard. The method detection limit was 0.10 microg L-1 for 76Se and 78Se and 0.13 microg L-1 for 77Se. Human serum samples from a case-control study investigating if selenium was associated with risk of colorectal adenoma were analyzed. The average selenium concentration for the control group (n=768) was 137.1 microg L-1 and the range was 73.4-305.5 microg L-1. The within-batch repeatability (a batch is ten samples) estimated from 182 replicate analyses was 6.3% coefficient of variation (CV), whereas the between-batch repeatability was 7.4% CV estimated from 361 replicates between batches. The method accuracy was evaluated by analysis of a human serum certified reference material (Seronorm Serum level II, Sero A/S, Norway). There was a fairly good agreement between the measured average of 145+/-3 microg L-1 (n=36) and the certified value of 136+/-9 microg L-1. In addition the method was successfully applied for analysis of zinc serum concentrations without further optimization. For the Seronorm certified reference material a value of 911+/-75 microg L-1 (n=31) for zinc was obtained, which corresponds well to the certified zinc value of 920+/-60 microg L-1
— id: 91604, year: 2005, vol: 381, page: 686, stat: Journal Article,

The prostate, lung, colon, and ovarian (PLCO) cancer screening trial: Status and promise
Andriole, Gerald L; Reding, Douglas; Hayes, Richard B; Prorok, Philip C; Gohagan, John K
2004 Jul-Aug;22(4):358-361, Urologic oncology
The Prostate, Lung, Cancer, and Ovarian Cancer Screening Trial is a randomized, multicenter, study evaluating whether screening for prostate, lung, colon, and ovarian cancer will reduce cancer-specific mortality. More than 155,000 participants have been identified and will be monitored through 2015. A biorepository of screened individuals and control participants has been created. Together, the data derived from the intervention and control arms and material in the biorepository provide a valuable resource to allow identification and testing of novel biomarkers for human disease
— id: 91596, year: 2004, vol: 22, page: 358, stat: Journal Article,

Occupation, pesticide exposure and risk of multiple myeloma
Baris, Dalsu; Silverman, Debra T; Brown, Linda Morris; Swanson, G Marie; Hayes, Richard B; Schwartz, Ann G; Liff, Jonathan M; Schoenberg, Janet B; Pottern, Linda M; Greenberg, Raymond S; Stewart, Patricia A
2004 Jun;30(3):215-222, Scandinavian journal of work environment & health
OBJECTIVES: This population-based case-control study examined the relationship between occupation, living or working on a farm, pesticide exposure, and the risk of multiple myeloma. METHODS: The study included 573 persons newly diagnosed with myeloma and 2131 controls. Information was obtained on sociodemographic factors, occupational history, and history of living and working on a farm. Occupational and industrial titles were coded by standardized classification systems. A job-exposure matrix was developed for occupational pesticide exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. RESULTS: Farmers and farm workers had odds ratios of 1.9 (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An odds ratio of 1.7 (95% CI 1.0-2.7) was observed for sheep farm residents or workers, whereas no increased risks were found for cattle, beef, pig, or chicken farm residents or workers. A modestly increased risk was observed for pesticides (OR 1.3, 95% CI 0.9-1.8). Significantly increased risks were found for pharmacists, dieticians and therapists (OR 6.1, 95% CI 1.7-22.5), service occupations (OR 1.3, 95% CI 1.02-1.7), roofers (OR 3.3, 95% CI 1.1-9.8), precision printing occupations (OR 10.1, 95% CI 1.03-99.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8), and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). CONCLUSIONS: A modest increased risk of multiple myeloma is suggested for occupational pesticide exposure. The increased risk for sheep farm residents or workers indicates that certain animal viruses may be involved in myeloma risk
— id: 91595, year: 2004, vol: 30, page: 215, stat: Journal Article,

Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review
Brennan, Paul; Lewis, Sarah; Hashibe, Mia; Bell, Douglas A; Boffetta, Paolo; Bouchardy, Christine; Caporaso, Neil; Chen, Chu; Coutelle, Christiane; Diehl, Scott R; Hayes, Richard B; Olshan, Andrew F; Schwartz, Stephen M; Sturgis, Erich M; Wei, Qingyi; Zavras, Athanasios I; Benhamou, Simone
2004 Jan 1;159(1):1-16, American journal of epidemiology
Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field
— id: 91584, year: 2004, vol: 159, page: 1, stat: Journal Article,

Impact of misclassification in genotype-exposure interaction studies: example of N-acetyltransferase 2 (NAT2), smoking, and bladder cancer
Deitz, Anne C; Rothman, Nathanial; Rebbeck, Timothy R; Hayes, Richard B; Chow, Wong-Ho; Zheng, Wei; Hein, David W; Garcia-Closas, Montserrat
2004 Sep;13(9):1543-1546, Cancer epidemiology biomarkers & prevention
Errors in genotype determination can lead to bias in the estimation of genotype effects and gene-environment interactions and increases in the sample size required for molecular epidemiologic studies. We evaluated the effect of genotype misclassification on odds ratio estimates and sample size requirements for a study of NAT2 acetylation status, smoking, and bladder cancer risk. Errors in the assignment of NAT2 acetylation status by a commonly used 3-single nucleotide polymorphism (SNP) genotyping assay, compared with an 11-SNP assay, were relatively small (sensitivity of 94% and specificity of 100%) and resulted in only slight biases of the interaction parameters. However, use of the 11-SNP assay resulted in a substantial decrease in sample size needs to detect a previously reported NAT2-smoking interaction for bladder cancer: 1,121 cases instead of 1,444 cases, assuming a 1:1 case-control ratio. This example illustrates how reducing genotype misclassification can result in substantial decreases in sample size requirements and possibly substantial decreases in the cost of studies to evaluate interactions
— id: 91597, year: 2004, vol: 13, page: 1543, stat: Journal Article,

Mortality from solid cancers among workers in formaldehyde industries
Hauptmann, Michael; Lubin, Jay H; Stewart, Patricia A; Hayes, Richard B; Blair, Aaron
2004 Jun 15;159(12):1117-1130, American journal of epidemiology
In industrial workers, formaldehyde exposure has been associated with cancer of the nasal cavities, nasopharynx, prostate, lung, and pancreas; however, these associations are inconsistent and remain controversial. Animals exposed to formaldehyde show excesses of nasal cancer. In an extended follow-up of a large cohort of formaldehyde-exposed workers, the authors evaluated mortality from solid cancers (1,921 deaths) among 25,619 workers (865,708 person-years) employed in 10 US formaldehyde-producing or -using facilities through 1994. Exposure assessment included quantitative estimates of formaldehyde exposure. Standardized mortality ratios and relative risks were calculated. Compared with that for the US population, mortality from solid cancers was significantly lower than expected among subjects exposed and nonexposed to formaldehyde (standardized mortality ratios = 0.91 and 0.78, respectively). Relative risks for nasopharyngeal cancer (nine deaths) increased with average exposure intensity, cumulative exposure, highest peak exposure, and duration of exposure to formaldehyde (p-trend = 0.066, 0.025, <0.001, and 0.147, respectively). Formaldehyde exposure did not appear to be associated with lung (744 deaths), pancreas (93 deaths), or brain (62 deaths) cancer. Although relative risks for prostate cancer (145 deaths) were elevated for some measures of formaldehyde exposure, the trend was inconsistent. In this cohort of formaldehyde-industry workers, some evidence was found of an exposure-response relation with mortality from nasopharyngeal cancer (based on small numbers) but not for cancers of the pancreas, brain, lung, or prostate
— id: 91593, year: 2004, vol: 159, page: 1117, stat: Journal Article,

Risk behaviours and benign prostatic hyperplasia
Kang, D; Andriole, G L; Van De Vooren, R C; Crawford, D; Chia, D; Urban, D A; Reding, D; Huang, W-Y; Hayes, R B
2004 Jun;93(9):1241-1245, BJU international
OBJECTIVE: To identify risk factors for benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: Medical history data, including reported urological conditions and treatments, and risk factor data were collected from 34 694 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial designed to evaluate methods for the early detection of cancer. RESULTS: Asian men had the lowest risks (odds ratio, 95% confidence interval) for nocturia (0.7, 0.5-0.9), physician-diagnosed BPH (0.3, 0.2-0.5) and transurethral prostatectomy (TURP, 0.2, 0.1-0.6), while risks for Whites and Blacks were similar for most measures of BPH. Greater alcohol intake was associated with decreased nocturia (P trend = 0.002), BPH (P trend < 0.001) and TURP (P trend < 0.001). Current tobacco use was associated with decreased nocturia (0.8, 0.7-0.9), BPH (0.7, 0.6-0.8) and TURP (0.6, 0.4-0.8) but dose-response patterns were weak. CONCLUSION: Asian-Americans have the lowest risk of clinical BPH. Alcohol and possibly cigarettes are related to a lower risk for BPH
— id: 91592, year: 2004, vol: 93, page: 1241, stat: Journal Article,

Hematotoxicity in workers exposed to low levels of benzene
Lan, Qing; Zhang, Luoping; Li, Guilan; Vermeulen, Roel; Weinberg, Rona S; Dosemeci, Mustafa; Rappaport, Stephen M; Shen, Min; Alter, Blanche P; Wu, Yongji; Kopp, William; Waidyanatha, Suramya; Rabkin, Charles; Guo, Weihong; Chanock, Stephen; Hayes, Richard B; Linet, Martha; Kim, Sungkyoon; Yin, Songnian; Rothman, Nathaniel; Smith, Martyn T
2004 Dec 3;306(5702):1774-1776, Science
Benzene is known to have toxic effects on the blood and bone marrow, but its impact at levels below the U.S. occupational standard of 1 part per million (ppm) remains uncertain. In a study of 250 workers exposed to benzene, white blood cell and platelet counts were significantly lower than in 140 controls, even for exposure below 1 ppm in air. Progenitor cell colony formation significantly declined with increasing benzene exposure and was more sensitive to the effects of benzene than was the number of mature blood cells. Two genetic variants in key metabolizing enzymes, myeloperoxidase and NAD(P)H:quinone oxidoreductase, influenced susceptibility to benzene hematotoxicity. Thus, hematotoxicity from exposure to benzene occurred at air levels of 1 ppm or less and may be particularly evident among genetically susceptible subpopulations
— id: 91599, year: 2004, vol: 306, page: 1774, stat: Journal Article,

Calcium intake and colorectal adenoma in a US colorectal cancer early detection program
Peters, Ulrike; Chatterjee, Nilanjan; McGlynn, Katherine A; Schoen, Robert E; Church, Timothy R; Bresalier, Robert S; Gaudet, Mia M; Flood, Andrew; Schatzkin, Arthur; Hayes, Richard B
2004 Nov;80(5):1358-1365, American journal of clinical nutrition
BACKGROUND: Calcium can reduce the risk of colorectal tumors by binding secondary bile and fatty acids, which leads to antiproliferative effects in the bowel, or by acting directly on the colonic epithelium, which affects differentiation and apoptosis. OBJECTIVE: We investigated calcium intake and risk of colon adenoma to evaluate the association of calcium intake with early stages of colorectal tumor development. DESIGN: We compared the supplemental and dietary calcium intakes of 3696 participants with histologically verified adenoma of the distal colon (ie, descending colon, sigmoid colon, or rectum) with the calcium intakes of 34 817 sigmoidoscopy-negative control participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Calcium intake was assessed at study entry with a 137-item food-frequency questionnaire and additional questions on the amount and duration of calcium supplement use. RESULTS: After adjustment for known risk factors, adenoma risk was lower by 12% for participants in the highest quintile of total calcium intake (>1767 mg/d) than for participants in the lowest quintile (<731 mg/d) (odds ratio: 0.88; 95% CI: 0.76, 1.02; P for trend = 0.04). The protective association between total calcium and colorectal adenoma was largely due to calcium supplement use, with a 27% decrease in adenoma risk for participants taking >1200 mg/d than for nonusers of supplements (odds ratio: 0.73; 95% CI: 0.56, 0.91; P for trend = 0.005). The protective associations of total and supplemental calcium were strongest for colon adenoma (descending and sigmoid colon). CONCLUSION: High calcium intake, particularly from supplements, is associated with a reduced risk of distal colorectal adenoma
— id: 91598, year: 2004, vol: 80, page: 1358, stat: Journal Article,

Association of genetic variants in the calcium-sensing receptor with risk of colorectal adenoma
Peters, Ulrike; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J; Schoen, Robert E; McGlynn, Katherine A; Church, Timothy R; Weissfeld, Joel L; Schatzkin, Arthur; Hayes, Richard B
2004 Dec;13(12):2181-2186, Cancer epidemiology biomarkers & prevention
OBJECTIVE: Evidence suggests that calcium prevents colorectal cancer, possibly mediated through the calcium-sensing receptor (CASR). We assessed the associations between CASR gene variants and risk for colorectal adenoma, a cancer precursor. We further investigated gene-diet interactions between the CASR variants and calcium intake on adenoma risk.METHODS: Individuals with advanced distal adenomas (n = 716) and controls with a negative sigmoidoscopy exam (n = 729) were randomly selected from participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Three nonsynonymous variants in the intracellular signaling region of CASR (A986S, R990G, Q1011E) were analyzed by Taqman.RESULTS: Compared with the most common diplotype (haplotype pair), the odds ratios for advanced adenoma were 0.80 [95% confidence interval (CI), 0.60-1.06], 0.79 (95% CI, 0.55-1.13), and 0.56 (95% CI, 0.36-0.88) for the other three common diplotypes (>5% frequency). Although calcium intake was inversely associated with adenoma risk, CASR diplotypes did not modify this association. However, the power to investigate interactions was limited.CONCLUSION: Variants in the CASR intracellular signaling region were significantly associated with the risk of advanced adenoma
— id: 91600, year: 2004, vol: 13, page: 2181, stat: Journal Article,

Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk
Peters, Ulrike; Hayes, Richard B; Chatterjee, Nilanjan; Shao, Wen; Schoen, Robert E; Pinsky, Paul; Hollis, Bruce W; McGlynn, Katherine A
2004 Apr;13(4):546-552, Cancer epidemiology biomarkers & prevention
OBJECTIVE: Vitamin D is a potential agent for the prevention of colorectal cancer possibly through mechanisms mediated by the vitamin D receptor (VDR). We investigated the association of circulating vitamin D metabolites and a genetic variant of the VDR gene with advanced colorectal adenoma, a precursor lesion of colorectal cancer. METHODS: Cases with advanced adenoma of the distal large bowel and gender- and ethnicity-matched controls with a negative sigmoidoscopy were randomly selected from participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Genotype analysis of the VDR TaqI polymorphism was completed on 763 cases and 774 controls. Serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured in a subset of 394 cases and 397 controls. RESULTS: Serum levels of 25(OH)D were inversely associated with advanced adenoma risk in women but not in men. Comparing those in the highest quintile with those in the lowest quintile, the risk for advanced adenoma decreased by 73% in women [odds ratio (OR) = 0.27, 95% confidence interval (95% CI) = 0.11-0.69; P for trend = 0.0002], while the risk did not decrease in men (OR = 1.10, 95% CI = 0.60-2.05; P for trend = 0.85). In women, 25(OH)D levels were significantly higher in current users of hormone replacement therapy (HRT) than in former or never HRT users. Neither serum 1,25(OH)(2)D nor VDR TaqI genotype was associated with advanced adenoma risk. CONCLUSION: Higher serum 25(OH)D levels were associated with decreased adenoma risk. Serum 1,25(OH)(2)D and VDR TaqI genotype were not associated with adenoma risk
— id: 91590, year: 2004, vol: 13, page: 546, stat: Journal Article,

SNPs, haplotypes, and cancer: applications in molecular epidemiology
Rebbeck, Timothy R; Ambrosone, Christine B; Bell, Douglas A; Chanock, Stephen J; Hayes, Richard B; Kadlubar, Fred F; Thomas, Duncan C
2004 May;13(5):681-687, Cancer epidemiology biomarkers & prevention
— id: 91591, year: 2004, vol: 13, page: 681, stat: Journal Article,

[No convincing evidence for a causal relationship between childhood nasopharyngeal radium irradiation and head-neck tumors or hormone-related disorders later in life; a retrospective cohort study]
Ronckers, C M; Verduijn, P G; Land, C E; Hayes, R B; Stovall, M; van Leeuwen, F E
2004 Sep 4;148(36):1775-1780, Nederlands tijdschrift voor geneeskunde
OBJECTIVE: To study the risk of malignant and benign tumours and hormone-related disorders among patients treated with nasopharyngeal radium irradiation for hypertrophic adenoid or hearing loss caused by otitis media serosa. DESIGN: Retrospective cohort study. METHOD: The medical record registries of 9 hospitals were used to identify a radium-exposed group (n = 5358) and a control group of unexposed patients (n = 5265), who were treated by an otolaryngologist in the period 1945-1981. The vital status of the subjects was determined using municipal resident registries, and the cause of death of decedents was retrieved from Statistics Netherlands (1950-1997). The data was also coupled with the Netherlands Cancer Registry (1989-1996). For the subjects still alive in 1997, the prevalence of relevant disorders was determined using a self-administered questionnaire and disorders reported by the participants were medically verified. The risk of disease in the radium group was then compared with that of the control group. RESULTS: The average radiation doses were 2.75, 0.109 and 0.015 Gy for nasopharynx, pituitary, and thyroid, respectively. There was no statistically significantly elevated risk for malignancies of the head and neck area (radium-exposed group; n = 14; control group: n = 11 (relative risk (RR): 1.2; 95% CI: 0.6-2.8)). Four of the five thyroid carcinomas were found in the radium-exposed group (RR: 3.8; 0.5-76). Elevated risks were observed for breast cancer (RR: 1.6; 0.9-2.7) and non-Hodgkin's lymphoma (RR: 2.7; 1.0-8.7). There was an increased risk for skin basal cell carcinoma (BCC) of the head and neck (odds ratio (OR): 2.6; 1.0-6.7), but the risk of BCC of other body parts was lower (OR: 0.3; 0.1-1.3). There were no major differences between radium and control subjects with respect to benign head and neck tumours (OR: 1.0; 0.5-1.7) or hormonal disorders. Exposed men reported slightly more fertility disorders than men in the control group (OR: 1.4; 1.0-2.1), but there was no clear dose-response relationship. CONCLUSION: After a mean follow-up of 31 years, there was no strong evidence for an elevated risk of head and neck tumours or hormone-related disorders in adulthood among subjects who had been treated with nasopharyngeal radium irradiation during childhood
— id: 91615, year: 2004, vol: 148, page: 1775, stat: Journal Article,

Detailed exposure assessment for a molecular epidemiology study of benzene in two shoe factories in China
Vermeulen, Roel; Li, Guilan; Lan, Qing; Dosemeci, Mustafa; Rappaport, Stephen M; Bohong, Xu; Smith, Martyn T; Zhang, Luoping; Hayes, Richard B; Linet, Martha; Mu, Ruidong; Wang, Lan; Xu, Jianing; Yin, Songnian; Rothman, Nathaniel
2004 Mar;48(2):105-116, Annals of occupational hygiene
OBJECTIVES: We carried out a detailed exposure assessment of benzene and toluene in two shoe factories in Tianjin, China. Our goal was to identify workers with a broad range of benzene exposures, for an epidemiologic study relating exposure to early biologic effects. METHODS: A comprehensive exposure survey program was initiated. Over a period of 16 months, 2783 personal solvent exposure samples were collected in two workplaces from 250 workers. Mixed-effects models were used to identify factors affecting exposure. Principal component analyses (PCA) and subsequent regression analyses on the scores of the identified principal components were used to relate potential co-exposures to various exposure sources present in the workplace. RESULTS: The mean benzene exposure level was 21.86 p.p.m. (10th-90th percentiles 5.23-50.63 p.p.m.) in the smaller shoe factory (factory A) and 3.46 p.p.m. (10th-90th percentiles 0.20-7.00 p.p.m.) in the larger shoe factory (factory B). Within-factory exposure levels differed among job titles and were higher for subjects directly involved in handling glues. In contrast, mean toluene levels were relatively similar in the two factories (factory A, 9.52 p.p.m.; factory B, 15.88 p.p.m.). A seasonal trend was identified for both benzene and toluene in factory B. This could be explained in part by changes in air movement and ventilation patterns occurring during the year. A seasonal trend was not present in the smaller shoe factory, where general ventilation was absent. Supplemental analysis showed that exposure levels to other hydrocarbons were low (< or =5 p.p.m.), less than 5% of their respective ACGIH threshold limit values, and generally comparable in the two factories. PCA showed that co-exposures in factory B could largely be explained by glue sources that were used in distinct areas in the workplace. CONCLUSIONS: We demonstrated the occurrence of a broad range of benzene exposure levels in two shoe manufacturing factories in Tianjin, China. Benzene and toluene exposures were determined in part by the degree of contact with glues, the benzene and toluene content of each glue, air movement and ventilation patterns. The availability of long-term monthly personal monitoring data provides an excellent opportunity to estimate individual exposures at different times during the 1 yr period of observation
— id: 91586, year: 2004, vol: 48, page: 105, stat: Journal Article,

Metabolic polymorphisms, smoking, and oral cancer in Puerto Rico
Xie, Heng; Hou, Lifang; Shields, Peter G; Winn, Deborah M; Gridley, Gloria; Bravo-Otero, Eleuterio; Diehl, Scott R; Bowman, Elise D; Brown, Linda M; Hayes, Richard B
2004 ;14(6):315-320, Oncology research
Genetic polymorphisms resulting in variation in metabolism of tobacco carcinogens may influence oral cancer risk. In a population-based case-control study in Puerto Rico, genotypes of CYP1A1, GSTM1, and GSTT1 were determined by a PCR-based method for 132 oral cancer patients and 143 control subjects. Genotype-associated risks were estimated by logistic regression. The null variant of GSTM1 was associated with a marginally significant decrease in oral cancer risk [odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.3-1.0, and P for trend = 0.09]. Risks increased with increasing cigarette use among subjects with the GSTM1-present genotype (P for trend <0.0001), rising to OR = 9.5, 95% CI = 3.0-30, among the heaviest cigarette users. In contrast, among subjects with the GSTM1-null genotype, risks did not clearly increase with increasing cigarette use (P for trend <0.61; OR = 1.8, 95% CI = 0.6-5.2 among the heaviest tobacco users). The GSTT1-null variant (OR = 1.0, 95% CI = 0.5-1.9) and CYP1A1(462Val) variant (OR = 0.9, 95% CI = 0.5-1.7) were not associated with the risk. Risks rose with increasing cigarette use in a similar manner for subjects with or without the CYP1A1(462Val) variant (P for interaction = 0.3) and for subjects with or without the GSTT1-null genotype (P for interaction = 0.4). In conclusion, cigarette use significantly increased the risk of oral cancer in this population. The GSTM1-present genotype was associated with higher tobacco-associated risk for oral cancer among heavy smokers than the null genotype
— id: 91594, year: 2004, vol: 14, page: 315, stat: Journal Article,

Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes
Zhang, Luoping; Hayes, Richard B; Guo, Weihong; McHale, Cliona M; Yin, Songnian; Wiencke, John K; Patrick O'Neill, J; Rothman, Nathaniel; Li, Gui-Lan; Smith, Martyn T
2004 Mar 14;558(1-2):63-74, Mutation research
1,3-Butadiene (BD) is an important industrial chemical and pollutant. Its ability to induce genetic damage and cause hematological malignancies in humans is controversial. We have examined chromosome damage by fluorescence in situ hybridization (FISH) and mutations in the HPRT gene in the blood of Chinese workers exposed to BD. Peripheral blood samples were collected and cultured from 39 workers exposed to BD (median level 2 ppm, 6 h time-weighted average) and 38 matched controls in Yanshan, China. No difference in the level of aneuploidy or structural changes in chromosomes 1, 7, 8, and 12 was detected in metaphase cells from exposed subjects in comparison with matched controls, nor was there an increase in the frequency of HPRT mutations in the BD-exposed workers. Because genetic polymorphisms in glutathione S-transferase (GST) enzymes and microsomal epoxide hydrolase (EPHX1) may affect the genotoxic effects of BD and its metabolites, we also related chromosome alterations and gene mutations to GSTT1, GSTM1 and EPHX1 genotypes. Overall, there was no effect of variants in these genotypes on numerical or structural changes in chromosomes 1, 7, 8 and 12 or on HPRT mutant frequency in relation to BD exposure, but the GST genotypes did influence background levels of both hyperdiploidy and HPRT mutant frequency. In conclusion, our data show no increase in chromosomal aberrations or HPRT mutations among workers exposed to BD, even in potentially susceptible genetic subgroups. The study is, however, quite small and the levels of BD exposure are not extremely high, but our findings in China do support those from a similar study conducted in the Czech Republic. Together, these studies suggest that low levels of occupational BD exposure do not pose a significant risk of genetic damage
— id: 91588, year: 2004, vol: 558, page: 63, stat: Journal Article,

Height and the survival of prostate cancer patients
Chen, Honglei; Miller, Barry A; Giovannucci, Edward; Hayes, Richard B
2003 Mar;12(3):215-218, Cancer epidemiology biomarkers & prevention
We investigated the associations between height and other anthropometric factors and the survival of 584 prostate cancer patients, initially recruited for a population-based, case-control study. During a median of 6.6 years of follow-up, 129 prostate cancer deaths and 153 deaths because of other causes were identified. After adjusting for age, cancer stage, and grade, the relative risk and 95% confident intervals for prostate cancer death were 1.0 (reference), 0.9 (0.6-1.4), 0.5 (0.3-0.9), and 0.6 (0.3-1.0) for patients whose heights were <1.75 m, 1.75-1.79 m, 1.80-1.84 m, and > or =1.85 m, respectively (P for trend = 0.01). Similar associations were found in subgroup analyses by cancer stage, cancer grade, age, race, and occupation-based socioeconomic status. However, height was not associated with death because of other causes. In addition, no significant associations were found between body mass index or weight and either prostate cancer death or death because of other causes. Our results suggest that greater height may be associated with better survival of prostate cancer patients
— id: 91574, year: 2003, vol: 12, page: 215, stat: Journal Article,

CYP2E1 and NQO1 genotypes, smoking and bladder cancer
Choi, Ji-Yeob; Lee, Kyoung-Mu; Cho, Soo-Hun; Kim, Soo-Woong; Choi, Han-Yong; Lee, Sang-Yoon; Im, Hyoung-June; Yoon, Ki Jung; Choi, Hwang; Choi, Inmi; Hirvonen, Ari; Hayes, Richard B; Kang, Daehee
2003 Jun;13(6):349-355, Pharmacogenetics
BACKGROUND: Cytochrome P450 2E1 (CYP2E1) and NAD(P)H:quinone oxidoreductase (NQO1) catalyze the activation of some environmental procarcinogens present in tobacco smoke (i.e. nitrosoamines and heterocyclic amines). We conducted a hospital based case-control study to evaluate the potential association between genetic polymorphisms of CYP2E1 (C1019T in the 5' flanking region) and NQO1 (C609T in exon 6) and bladder cancer risk in Asian population. METHODS: The study population was comprised of 218 histologically confirmed prevalent bladder cancer cases and 199 controls without cancer or systemic illness. PCR-restriction fragment length polymorphism based methods were used for the genotyping analyses and unconditional logistic regression model for the statistical evaluations. RESULTS: The risk of bladder cancer increased with the amount of smoking (P for trend < 0.01). The frequency of CYP2E1 c1/c1 genotype was significantly higher in bladder cancer patients (57.9%) than in the controls (47.9%) (OR = 1.8, 95% CI = 1.1-2.9). Similarly, the NQO1 C/C genotypes were significantly more prevalent in the patients (45.8%) than in the controls (37.6%) (OR = 1.6, 95% CI = 1.0-2.7). The risk for bladder cancer increased with the number of the putative risk genotypes (P for trend = 0.03); the most remarkable risk was observed for heavy smokers with both CYP2E1 c1/c1 and NQO1 C/C genotypes (OR = 13.8, 95% CI = 3.9-48.6) when compared to non/light smokers with other genotypes. CONCLUSION: Our findings suggest that CYP2E1 and NQO1 genotypes may play an important role in development of smoking related bladder cancer among Korean men
— id: 91578, year: 2003, vol: 13, page: 349, stat: Journal Article,

Sugarcane farming, occupational solvent exposures, and the risk of oral cancer in Puerto Rico
Coble, Joseph B; Brown, Linda Morris; Hayes, Richard B; Huang, Wen-Yi; Winn, Deborah M; Gridley, Gloria; Bravo-Otero, Eleuterio; Fraumeni, Joseph F Jr
2003 Aug;45(8):869-874, Journal of occupational & environmental medicine
The work history information from a population-based case-control study conducted in Puerto Rico was analyzed using a job exposure matrix to investigate the relationship between occupational exposures and cancers of the oral cavity or pharynx. After adjustment for age, alcohol, smoking, and residence in a logistic model, the risk for cancer of the oral cavity, but not the pharynx, was significantly elevated among farm workers in the sugarcane industry (OR = 4.4, 95% CI = 1.4-13.6). An exposure-response trend was seen for cumulative exposure to solvents, with an OR = 3.2 (95% CI = 0.8-12.6) in the highest exposure category. The overall contribution to the risk of cancer of the oral cavity or pharynx associated with occupational exposures in Puerto Rico appears to be small, however, the elevated risks were seen among sugarcane farmers and subjects with high cumulative exposure to solvents
— id: 91579, year: 2003, vol: 45, page: 869, stat: Journal Article,

Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries
Hauptmann, Michael; Lubin, Jay H; Stewart, Patricia A; Hayes, Richard B; Blair, Aaron
2003 Nov 5;95(21):1615-1623, Journal of the National Cancer Institute
BACKGROUND: Many U.S. factory workers are exposed to formaldehyde. Although increased risks for leukemia have been found in medical workers and other professionals exposed to formaldehyde, studies in industrial workers, who are thought to have higher exposures, have shown inconsistent associations. We extended follow-up of a cohort of industrial workers to evaluate the association between formaldehyde exposure and lymphohematopoietic cancers. METHODS: The cohort consisted of 25 619 workers (865 708 person-years) employed before January 1, 1966, at one of 10 U.S. industrial plants and followed through December 31, 1994. We analyzed formaldehyde exposure (peak exposure, average exposure intensity, cumulative exposure, and duration of exposure) and mortality from lymphohematopoietic malignancies using standardized mortality ratios and relative risks and 95% confidence intervals (CIs) based on Poisson regression. Statistical tests were two-sided. RESULTS: Among the cohort, there were 178 deaths from lymphohematopoietic malignancies. Relative risks for leukemia (69 deaths), particularly for myeloid leukemia (30 deaths), increased with formaldehyde exposure. Compared with workers exposed to low peak levels of formaldehyde (0.1-1.9 ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25) and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of 2.0-3.9 ppm and > or = 4.0 ppm, respectively (P(trend) =.009). Compared with workers exposed to low levels of average exposure intensity of formaldehyde (0.1-0.4 ppm), workers exposed to 0.5-0.9 ppm and > or = 1.0 ppm average intensity had relative risks of 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03), respectively (P(trend) =.088). The relative risk for leukemia was not associated with cumulative exposure but was weakly associated with duration of exposure. Relative risks for Hodgkin's disease also increased with formaldehyde exposure. CONCLUSIONS: Exposure to formaldehyde may cause leukemia, particularly myeloid leukemia, in humans. However, results from other investigations are mixed, suggesting caution in drawing definitive conclusions
— id: 91582, year: 2003, vol: 95, page: 1615, stat: Journal Article,

Alcohol concentration and risk of oral cancer in Puerto Rico
Huang, Wen-Yi; Winn, Deborah M; Brown, Linda M; Gridley, Gloria; Bravo-Otero, Eleuterio; Diehl, Scott R; Fraumeni, Joseph F Jr; Hayes, Richard B
2003 May 15;157(10):881-887, American journal of epidemiology
Alcohol consumption is a major risk factor for cancers of the mouth and pharynx (oral cancer), but the differential risks by beverage type are unclear. In this 1992-1995 study, the authors examined oral cancer risk in Puerto Rico, comparing alcohol intake among 286 male cases aged 21-79 years and 417 population-based male controls, frequency matched by age. Heavy consumers of liquor (>/=43 drinks per week) had strongly increased risks of oral cancer (odds ratio = 6.4, 95% confidence interval: 2.4, 16.8); beer/wine showed only modest effects. Among liquor drinkers, risks were consistently greater for those who drank straight (undiluted) liquor than for those who usually drank mixed (diluted) liquor (odds ratio = 4.0, 95% confidence interval: 2.4, 6.7). Risks associated with combined exposure to tobacco were also more pronounced when subjects drank liquor straight. The elevated risks associated with drinking homemade rum were similar to those for other types of liquor. These results suggest that alcohol concentration is a risk factor for oral cancer independent of the total quantity of alcohol consumed
— id: 91577, year: 2003, vol: 157, page: 881, stat: Journal Article,

Multiple biomarkers study in painters in a shipyard in Korea
Lee, Kyoung-Ho; Ichiba, Masayoshi; Zhang, Jiusong; Tomokuni, Katsumaro; Hong, Yun-Chul; Ha, Mina; Kwon, Ho Jang; Koh, Sang-Back; Choi, Hong-Ryul; Lee, Kwan-Hee; Park, Chung-Gyu; Cho, Soo-Hun; Hirvonen, Ari; Strickland, Paul T; Vermeulen, Roel; Hayes, Richard B; Kang, Daehee
2003 Sep 9;540(1):89-98, Mutation research
Shipbuilding workers are exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs). A limited number of studies have been conducted to evaluate biomarkers related to PAH exposure in painters in the shipyard industry. We examined this in 208 workers recruited from a shipyard located in South Korea. Employees were grouped into three exposure groups: (1) 111 painters using coal tar paints, (2) 70 painters using general paints, and (3) 27 on-site controls using no paints. Levels of urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy. Glutathione S-transferase (GST) M1 and T1 genotypes were assessed by a multiplex polymerase chain reaction (PCR)-based method, aromatic-DNA adducts in peripheral white blood cells were measured by 32P-postlabeling, and glycophorin A (GPA) variant frequencies in red blood cells were assessed by flow cytometry. Information on demographic characteristics, smoking habits, diet, job title and use of personal protective equipment (e.g. respiratory and dermal) were collected by self-administered questionnaire. Average urinary 1-OHPG levels in coal tar paint (2.24 micromol/mol creatinine) and general paint (1.38 micromol/mol creatinine) users were significantly higher than in on-site controls (0.62 micromol/mol creatinine) (P<0.001). Paint use, irrespective of the type of paints, and smoking (yes/no) were positively associated with urinary 1-OHPG levels, whereas green tea consumption (yes/no) was negatively associated with the 1-OHPG levels. No significant effect in the 1-OHPG levels were observed for the GSTM1 and GSTT1 genotypes. Aromatic-DNA adduct levels tended to be higher in coal tar paint users (P = 0.06) and painters (P = 0.07) compared to on-site controls. No differences in adduct levels were observed, between the two groups of painters, and the combined group showed greater adduct levels than on-site controls (P = 0.05). GPA mutation frequencies measured in 55 individuals with MN heterozygote genotypes were not significantly different among the three exposure groups, and no correlation was observed between urinary 1-OHPG levels and aromatic-DNA adducts or GPA mutation frequency. These results suggest that painters in the shipyard were exposed to significant amounts of PAHs and possibly to other genotoxic aromatic compounds, and that urinary 1-OHPG may be a potential biomarker of PAH exposure in this population
— id: 91580, year: 2003, vol: 540, page: 89, stat: Journal Article,

Epidemiologic considerations to assess altered DNA methylation from environmental exposures in cancer
Moore, Lee E; Huang, Wen-Yi; Chung, Joyce; Hayes, Richard B
2003 Mar;983:181-196, Annals of the New York Academy of Sciences
Epidemiologic studies in human populations have identified a broad spectrum of risk factors for cancer. Gene-damaging agents have been a primary focus of cancer epidemiology; however, all xenobiotics do not interact with DNA directly. Some exogenous agents induce epigenetic changes. In view of this, markers that measure changes to the epigenome must also be incorporated into molecular epidemiologic studies. We review the current understanding of the impact of exogenous agents including: micronutrients, chemotherapeutic agents, metals, and others, on DNA methylation. Two categories of genes are described: (1) genes that can alter susceptibility to aberrant DNA methylation and (2) genes that increase susceptibility to cancer when they are silenced through DNA methylation. Methods for incorporating markers of DNA methylation status into etiologic investigations of the impact of environmental exposures on disease (e.g., cancer) are discussed
— id: 91575, year: 2003, vol: 983, page: 181, stat: Journal Article,

Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme
Peters, Ulrike; Sinha, Rashmi; Chatterjee, Nilanjan; Subar, Amy F; Ziegler, Regina G; Kulldorff, Martin; Bresalier, Robert; Weissfeld, Joel L; Flood, Andrew; Schatzkin, Arthur; Hayes, Richard B
2003 May 3;361(9368):1491-1495, Lancet
BACKGROUND: Although dietary fibre has been reported to have no association with colorectal adenoma and cancer, in some studies this topic remains controversial. METHODS: We used a 137-item food frequency questionnaire to assess the relation of fibre intake and frequency of colorectal adenoma. The study was done within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomised controlled trial designed to investigate methods for early detection of cancer. In our analysis, we compared fibre intake of 33971 participants who were sigmoidoscopy-negative for polyps, with 3591 cases with at least one histologically verified adenoma in the distal large bowel (ie, descending colon, sigmoid colon, or rectum). Odds ratios were estimated by logistic regression analysis. FINDINGS: High intakes of dietary fibre were associated with a lower risk of colorectal adenoma, after adjustment for potential dietary and non-dietary risk factors. Participants in the highest quintile of dietary fibre intake had a 27% (95% CI 14-38, p(trend)=0.002) lower risk of adenoma than those in the lowest quintile. The inverse association was strongest for fibre from grains and cereals and from fruits. Risks were similar for advanced and non-advanced adenoma. Risk of rectal adenoma was not significantly associated with fibre intake. INTERPRETATION: Dietary fibre, particularly from grains, cereals, and fruits, was associated with decreased risk of distal colon adenoma
— id: 91576, year: 2003, vol: 361, page: 1491, stat: Journal Article,

Predictors of advanced proximal neoplasia in persons with abnormal screening flexible sigmoidoscopy
Pinsky, Paul F; Schoen, Robert E; Weissfeld, Joel L; Bresalier, Robert S; Hayes, Richard B; Gohagan, John K
2003 Mar;1(2):103-110, Clinical Gastroenterology & Hepatology
BACKGROUND & AIMS: The relationship between distal and proximal colonic findings is uncertain. Thus, there is no consensus on which findings on screening flexible sigmoidoscopy should trigger colonoscopy. METHODS: We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between distal and proximal colonic findings. RESULTS: A total of 8802 subjects had an abnormal baseline sigmoidoscopy and colonoscopy follow-up. Subjects with <10-mm single or multiple tubular adenomas had similar risks for advanced proximal neoplasia as subjects with hyperplastic polyps or other benign lesions (3%-5%). Subjects with large (>or=10 mm), villous, or severely dysplastic distal adenomas had similarly elevated risks for advanced proximal neoplasia (11%-12%). Multivariate logistic modeling showed a significantly increased risk for advanced proximal neoplasia associated with the presence of a large tubular (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.0-3.4) or villous distal adenoma (OR, 2.7; 95% CI, 2.1-3.5) but not with the presence of one (OR, 1.05; 95% CI, 0.8-1.3) or multiple (OR, 0.8; 95% CI, 0.5-1.2) <10-mm tubular distal adenomas. CONCLUSIONS: Among subjects with a polypoid lesion on screening flexible sigmoidoscopy, those with small tubular distal adenomas are at similar risk for advanced proximal neoplasia as those without distal adenomas. Subjects with a large, villous, or dysplastic distal adenoma are at increased risk. A strategy that encourages individuals with small tubular adenomas on sigmoidoscopy to undergo follow-up colonoscopy and excludes those with nonadenomatous lesions is of questionable validity, because both groups are at similar risk for advanced proximal neoplasia
— id: 91587, year: 2003, vol: 1, page: 103, stat: Journal Article,

Why do Black Americans have a higher risk of pancreatic cancer than White Americans?
Silverman, Debra T; Hoover, Robert N; Brown, Linda M; Swanson, G Marie; Schiffman, Mark; Greenberg, Raymond S; Hayes, Richard B; Lillemoe, Keith D; Schoenberg, Janet B; Schwartz, Ann G; Liff, Jonathan; Pottern, Linda M; Fraumeni, Joseph F Jr
2003 Jan;14(1):45-54, Epidemiology
BACKGROUND: For several decades, the incidence of pancreatic cancer has been 50% to 90% higher among blacks than among whites in the United States. The purpose of this study was to identify risk factors that may contribute to this racial disparity. METHODS: We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. In-person interviews were exclusively with subjects (526 cases and 2153 population controls), rather than with next of kin. RESULTS: The determinants of the higher incidence of pancreatic cancer among blacks than among whites differed by sex. Among men, established risk factors (, cigarette smoking, long-term diabetes mellitus, family history of pancreatic cancer) account for 46% of the disease in blacks and 37% in whites, potentially explaining all but 6% of the excess risk among blacks. Among women, however, other factors appear to contribute to the racial disparity, notably moderate/heavy alcohol consumption (>7 drinks per week) and elevated body mass index (above the first quartile). When these less accepted risk factors were combined with the established risk factors, 88% of the disease in black women and 47% in white women were explained, potentially accounting for all of the excess risk among blacks in our female study population. CONCLUSIONS: Among men, the established risk factors (mainly cigarette smoking and diabetes mellitus) explain almost the entire black/white disparity in incidence. Among women, however, other factors appear to contribute to the racial disparity, notably moderate/heavy alcohol consumption and elevated body mass index. In the absence of these factors, pancreatic cancer incidence rates among blacks probably would not exceed those among whites of either sex
— id: 91573, year: 2003, vol: 14, page: 45, stat: Journal Article,

Serum selenium and risk of prostate cancer in U.S. blacks and whites
Vogt, Tara M; Ziegler, Regina G; Graubard, Barry I; Swanson, Christine A; Greenberg, Raymond S; Schoenberg, Janet B; Swanson, G Marie; Hayes, Richard B; Mayne, Susan T
2003 Feb 20;103(5):664-670, International journal of cancer
Prostate cancer is the fourth most common cancer in men worldwide and the most common cancer in men in the United States, with reported incidence rates for U.S. blacks being the highest in the world. The etiology of prostate cancer and an explanation for the racial disparity in incidence in the United States remain elusive. Epidemiologic studies suggest that selenium, an essential trace element, may protect against the disease. To further explore this hypothesis, we measured serum selenium in 212 cases and 233 controls participating in a multicenter, population-based case-control study that included comparable numbers of U.S. black and white men aged 40-79 years. Serum selenium was inversely associated with risk of prostate cancer (comparing highest to lowest quartiles, OR = 0.71, 95% CI 0.39-1.28; p for trend = 0.11), with similar patterns seen in both blacks and whites. Cubic regression spline analysis of continuous serum selenium indicated a reduced risk of prostate cancer above concentrations of 0.135 microg/ml (median among controls) compared to a reference value set at the median of the lowest selenium quartile. Because both the selenoenzyme GPX and vitamin E can function as antioxidants, we also explored their joint effect. Consistent with other studies, the inverse association with selenium was strongest among men with low serum alpha-tocopherol concentrations. In conclusion, our results suggest a moderately reduced risk of prostate cancer at higher serum selenium concentrations, a finding that can now be extended to include U.S. blacks. Since selenium exposure varies widely throughout the world, further research on optimal concentrations for cancer prevention is justified
— id: 91572, year: 2003, vol: 103, page: 664, stat: Journal Article,

Occurrence of NKX3.1 C154T polymorphism in men with and without prostate cancer and studies of its effect on protein function
Gelmann, Edward P; Steadman, David J; Ma, Jing; Ahronovitz, Natalie; Voeller, H James; Swope, Sheridan; Abbaszadegan, Mohammed; Brown, Kevin M; Strand, Kate; Hayes, Richard B; Stampfer, Meir J
2002 May 1;62(9):2654-2659, Cancer research
NKX3.1, a member of the NK class of homeodomain proteins, is expressed primarily in the adult prostate and has growth suppression and differentiating effects in prostate epithelial cells. A C-->T polymorphism at nucleotide 154 (NKX3.1 C154T) is present in approximately 11% of healthy men with equal distribution among whites and blacks. In a cohort of 1253 prostate cancer patients and age-matched controls, the presence of the polymorphism was associated with a 1.8-fold risk of having stage C or D prostate cancer or Gleason score > or =7 (confidence interval, 1.01-3.22). The NKX3.1 C154T polymorphism codes for a variant protein that contains an arginine-to-cysteine substitution at amino acid 52 (R52C) adjacent to a protein kinase C phosphorylation site at serine 48. Substitution of cysteine for arginine 52 or of alanine for serine 48 (S48A) reduced phosphorylation at serine 48 in vitro and in vivo. Phosphorylation of wild-type NKX3.1, but not of NKX3.1 R52C or NKX3.1 S48A, diminished binding in vitro to a high-affinity DNA binding sequence. NKX3.1 also serves as a transcriptional coactivator of serum response factor. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate to phosphorylate NKX3.1 had no effect on NKX3.1 coactivation of serum response factor. Neither the R52C nor the S48A substitution affected serum response factor coactivation by NKX3.1 We conclude that the polymorphic NKX3.1 allele codes for a variant protein with altered DNA binding activity that may affect prostate cancer risk
— id: 91564, year: 2002, vol: 62, page: 2654, stat: Journal Article,

Whole blood cryopreservation in epidemiological studies
Hayes, Richard B; Smith, Craig O; Huang, Wen-Yi; Read, Yvonne; Kopp, William C
2002 Nov;11(11):1496-1498, Cancer epidemiology biomarkers & prevention
Standardized and cost-effective biological sample collection, processing, and storage procedures are needed in large-scale epidemiological studies to provide material for testing a broad range of etiological hypotheses. One component of sample collection in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial involves shipment of blood in acid-citrate-dextrose anticoagulant to a central processing laboratory, where 10% DMSO is added, and whole blood aliquots are cryopreserved. A single technician is able to routinely process 50-60 samples/day. Tests conducted to evaluate potential uses of cryopreserved whole blood showed successful EBV transformation (>90%, up to 20 months of storage). In addition, lymphocytes maintained good viability and stable T-cell:B-cell ratios, and T cells maintained the capacity to proliferate in response to solid phase anti-CD3/CD28 plus interleukin 2. Whole blood cryopreservation is a cost-effective approach to large-scale storage of viable cells in epidemiological studies
— id: 91570, year: 2002, vol: 11, page: 1496, stat: Journal Article,

A geographic analysis of prostate cancer mortality in the United States, 1970-89
Jemal, Ahmedin; Kulldorff, Martin; Devesa, Susan S; Hayes, Richard B; Fraumeni, Joseph F Jr
2002 Sep 10;101(2):168-174, International journal of cancer
The recently published atlas of cancer mortality in the United States revealed that prostate cancer mortality rates were elevated among white men in the Northwest, the Rocky Mountain states, the north-central area, New England and the South Atlantic area, and among black men in the South Atlantic area. Here we determine whether the elevated regional rates were statistically different from rates in the rest of the country and whether the pattern can be explained by selected regional characteristics. A spatial scan statistic was applied to county-based mortality data from 1970 through 1989 to identify geographic clusters of the elevated rates for prostate cancer. Five clusters of elevated mortality were detected in white men (p < 0.005) and 3 in black men (p = 0.0001-0.056). For white men, the primary cluster was in the northwestern quadrant, followed by clusters in New England, the eastern part of the north-central area, the mid-Atlantic states and the South Atlantic area, whereas for black men the primary cluster was in the South Atlantic area, followed by clusters in Alabama and the eastern part of the north-central area. Further analyses of these clusters revealed several significant subclusters (p < 0.05). None of the selected demographic and socioeconomic factors, separately or collectively, accounted for the primary clusters in the U.S. white and black populations. The patterns observed could not be attributed to selected demographic or socioeconomic characteristics but should provide leads for further study into the risk factors and the medical or reporting practices that may contribute to geographic variation in mortality from prostate cancer
— id: 91568, year: 2002, vol: 101, page: 168, stat: Journal Article,

Sinonasal cancer and occupational exposures: a pooled analysis of 12 case-control studies
Luce, Daniele; Leclerc, Annette; Begin, Denis; Demers, Paul A; Gerin, Michel; Orlowski, Ewa; Kogevinas, Manolis; Belli, Stefano; Bugel, Isabelle; Bolm-Audorff, Ulrich; Brinton, Louise A; Comba, Pietro; Hardell, Lennart; Hayes, Richard B; Magnani, Corrado; Merler, Enzo; Preston-Martin, Susan; Vaughan, Thomas L; Zheng, Wei; Boffetta, Paolo
2002 Mar;13(2):147-157, Cancer causes & control. ccc
OBJECTIVE: In order to examine the associations between sinonasal cancer and occupational exposures other than wood dust and leather dust, the data from 12 case-control studies conducted in seven countries were pooled and reanalyzed. METHODS: The pooled data set included 195 adenocarcinoma cases (169 men and 26 women), 432 squamous cell carcinomas (330 men and 102 women), and 3136 controls (2349 men and 787 women). Occupational exposures to formaldehyde, silica dust, textile dust, coal dust, flour dust, asbestos, and man-made vitreous fibers were assessed with a job-exposure matrix. Odds ratios (ORs) were adjusted for age, study, wood dust, and leather dust, or other occupational exposures when relevant. 95% confidence intervals (CIs) were estimated by unconditional logistic regression. RESULTS: A significantly increased risk of adenocarcinoma was associated with exposure to formaldehyde. The ORs for the highest level of exposure were 3.0 (Cl = 1.5-5.7) among men and 6.2 (CI=2.0-19.7) among women. An elevated risk of squamous cell carcinoma was observed among men (OR=2.5, CI=0.6-10.1) and women (OR = 3.5, CI = 1.2-10.5) with a high probability of exposure to formaldehyde. Exposure to textile dust was associated with non-significantly elevated risk of adenocarcinoma, among women only: the OR for the high level of cumulative exposure was 2.5 (CI = 0.7-9.0). High level of asbestos exposure was associated with a significantly increased risk of squamous cell carcinoma among men (OR = 1.6, CI = 1.1-2.3). CONCLUSIONS: The results of this pooled analysis support the hypothesis that occupational exposure to formaldehyde increases the risk of sinonasal cancer, particularly of adenocarcinoma. They also indicate an elevated risk of adenocarcinoma among women exposed to textile dust, and suggest that exposure to asbestos may increase the risk of squamous cell carcinoma
— id: 91561, year: 2002, vol: 13, page: 147, stat: Journal Article,

Non-linear production of benzene oxide-albumin adducts with human exposure to benzene
Rappaport, Stephen M; Yeowell-O'Connell, Karen; Smith, Martyn T; Dosemeci, Mustafa; Hayes, Richard B; Zhang, Luoping; Li, Guilan; Yin, Songnian; Rothman, Nathaniel
2002 Oct 5;778(1-2):367-374, Journal of chromatography. B. Analytical technologies in the biomedical & life sciences
Benzene is initially metabolized to benzene oxide, which either undergoes further metabolism or reacts with macromolecules including proteins. Previously reported levels of benzene oxide-albumin adducts (BO-Alb) are analyzed from 30 workers exposed to 0.2-302 ppm benzene and 43 controls from Shanghai, China. Although both exposed workers and controls had significant levels of BO-Alb in their blood, exposed subjects' adduct levels (GM=378 pmol/g protein) were much greater than those of controls (GM=115 pmol/g protein). When the natural logarithm of the BO-Alb level was regressed upon the natural logarithm of exposure among the 30 exposed subjects, a strong effect of benzene exposure was observed (R(2)=0.612; p<0.0001). Because the slope of the relationship between BO-Alb and benzene exposure was significantly less than one in log-space, we infer that production of benzene oxide was less than proportional to benzene exposure. Since benzene is a substrate for CYP2E1, these results are consistent with saturation of CYP450 metabolism. They indicate that deviations from linear metabolism began at or below benzene exposures of 10 ppm and that pronounced saturation was apparent at 40-50 ppm. To our knowledge, this is the first study to investigate the linearity of human metabolism of a carcinogen based upon protein adducts
— id: 91569, year: 2002, vol: 778, page: 367, stat: Journal Article,

Late health effects of childhood nasopharyngeal radium irradiation: nonmelanoma skin cancers, benign tumors, and hormonal disorders
Ronckers, Cecile M; Land, Charles E; Hayes, Richard B; Verduijn, Pieter G; Stovall, Marilyn; van Leeuwen, Flora E
2002 Dec;52(6):850-858, Pediatric research
Nasopharyngeal radium irradiation (NRI) was widely used from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for benign tumors, nonmelanoma skin cancer, thyroid disorders, and conditions related to regulatory control of anterior pituitary hormones, such as growth and reproductive characteristics. We conducted a retrospective cohort study in 3,440 NRI-exposed and 3,088 nonexposed subjects, who as children were treated at nine ear, nose and throat clinics in The Netherlands between 1945 and 1981. Based on information from original medical records, we traced vital status through follow-up at municipal population registries. Disease status (including medical confirmation) and indicators of pituitary gland radiation damage were assessed from a self-administered questionnaire in 1997. The average radiation doses were 11, 7, and 1.5 cGy for pituitary, parotid, and thyroid gland, respectively, and 3.2 cGy for the facial skin. Among exposed subjects, 23 benign head and neck tumors were observed, compared with 21 among nonexposed subjects. Elevated risk of basal cell carcinoma of the head and neck area was observed in exposed subjects (odds ratio = 2.6; 95% confidence interval: 1.0-6.7). Exposed and nonexposed groups did not differ substantially with regard to thyroid disorders, height, and reproductive characteristics, although exposed males more frequently reported a history of fertility problems compared with nonexposed males (odds ratio = 1.4; 95% confidence interval: 1.0-2.1). We found no evidence of highly elevated risk of benign head and neck tumors, nonmelanoma skin cancer, thyroid disorders, or indicators of pituitary radiation damage after childhood NRI in The Netherlands
— id: 91571, year: 2002, vol: 52, page: 850, stat: Journal Article,

Cancer incidence after nasopharyngeal radium irradiation
Ronckers, Cecile M; Van Leeuwen, Flora E; Hayes, Richard B; Verduijn, Pieter G; Stovall, Marilyn; Land, Charles E
2002 Sep;13(5):552-560, Epidemiology
BACKGROUND: From 1940 until 1970, nasopharyngeal radium irradiation was used to treat children and military personnel suffering from Eustachian tube failure attributable to local lymphoid hyperplasia. METHODS: We studied cancer incidence in a cohort of 4339 Dutch patients treated with nasopharyngeal radium irradiation, mostly in childhood, and 4104 frequency-matched nonexposed subjects. Average doses to the nasopharynx, pituitary gland, brain, and thyroid gland were 275, 10.9, 1.8, and 1.5 cGy, respectively. We assessed cancer incidence from cancer registry linkage (1989-1996), self-report including medical verification (1945-1988), and death certificates (1945-1996). RESULTS: During 18-50 years of follow-up, four thyroid malignancies (standardized incidence ratio [SIR] = 2.8; 95% confidence interval [CI] = 0.8-7.2) and five malignant brain tumors (SIR = 1.3; CI = 0.4-3.1) were observed. Increased risks were observed for malignancies of lymphoproliferative and hematopoietic origin (SIR = 1.9; CI = 1.2-2.8) and breast cancer (SIR = 1.5; CI = 1.1-2.1). Strong dose-response trends could not be demonstrated for any cancer outcome, although relative risk estimates were elevated in the highest-dose category for head and neck cancer and breast cancer. CONCLUSIONS: These data provide little evidence for a high excess risk of cancer associated with nasopharyngeal radium irradiation treatment as applied in the Netherlands. Inconsistent findings across studies and public concern warrant the continuing follow-up of available cohorts
— id: 91567, year: 2002, vol: 13, page: 552, stat: Journal Article,

DNA banking for epidemiologic studies: a review of current practices
Steinberg, Karen; Beck, Jeanne; Nickerson, Deborah; Garcia-Closas, Montserrat; Gallagher, Margaret; Caggana, Michele; Reid, Yvonne; Cosentino, Mark; Ji, Jay; Johnson, Delene; Hayes, Richard B; Earley, Marie; Lorey, Fred; Hannon, Harry; Khoury, Muin J; Sampson, Eric
2002 May;13(3):246-254, Epidemiology
To study genetic risk factors for common diseases, researchers have begun collecting DNA specimens in large epidemiologic studies and surveys. However, little information is available to guide researchers in selecting the most appropriate specimens. In an effort to gather the best information for the selection of specimens for these studies, we convened a meeting of scientists engaged in DNA banking for large epidemiologic studies. In this discussion, we review the information presented at that meeting in the context of recent published information. Factors to be considered in choosing the appropriate specimens for epidemiologic studies include quality and quantity of DNA, convenience of collection and storage, cost, and ability to accommodate future needs for genotyping. We focus on four types of specimens that are stored in these banks: (1) whole blood preserved as dried blood spots; (2) whole blood from which genomic DNA is isolated, (3) immortalized lymphocytes from whole blood or separated lymphocytes, prepared immediately or subsequent to cryopreservation; and (4) buccal epithelial cells. Each of the specimens discussed is useful for epidemiologic studies according to specific needs, which we enumerate in our conclusions
— id: 91562, year: 2002, vol: 13, page: 246, stat: Journal Article,

Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites
Vogt, T M; Mayne, S T; Graubard, B I; Swanson, C A; Sowell, A L; Schoenberg, J B; Swanson, G M; Greenberg, R S; Hoover, R N; Hayes, R B; Ziegler, R G
2002 Jun 1;155(11):1023-1032, American journal of epidemiology
Epidemiologic studies investigating the relation between individual carotenoids and risk of prostate cancer have produced inconsistent results. To further explore these associations and to search for reasons prostate cancer incidence is over 50% higher in US Blacks than Whites, the authors analyzed the serum levels of individual carotenoids in 209 cases and 228 controls in a US multicenter, population-based case-control study (1986-1989) that included comparable numbers of Black men and White men aged 40-79 years. Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. For all carotenoids, patterns were similar for Blacks and Whites. However, in both the controls and the Third National Health and Nutrition Examination Survey, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence. In conclusion, the results, though not statistically significant, suggest that serum lycopene is inversely related to prostate cancer risk in US Blacks and Whites
— id: 91565, year: 2002, vol: 155, page: 1023, stat: Journal Article,

Folate intake, serum homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T genotype are not associated with oral cancer risk in Puerto Rico
Weinstein, Stephanie J; Gridley, Gloria; Harty, Lea C; Diehl, Scott R; Brown, Linda M; Winn, Deborah M; Bravo-Otero, Eleuterio; Hayes, Richard B
2002 Apr;132(4):762-767, Journal of nutrition
We examined the relationships between folate and methionine intake, serum homocysteine levels (as a biomarker for folate metabolism), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype and risk of oral cancer in a population-based, case-control study in Puerto Rico. Structured questionnaires were used to collect information on demographic factors, usual adult diet, and tobacco and alcohol use. Oral epithelial cells and blood samples were collected from a subset of subjects. Analyses were conducted by logistic regression, adjusting for age, sex, lifetime smoking and lifetime alcohol intake, with the following numbers of cases/controls, respectively: dietary data (341/521); MTHFR genotype (148/149); and homocysteine (60/90). Although increased folate intake was associated with decreased oral cancer risk [adjusted odds ratio (OR) in highest vs. lowest quartile = 0.6, 95% confidence interval (CI): 0.4, 1.0, P(trend) = 0.05)], this finding was due almost entirely to folate intake from fruit (adjusted OR = 0.4, 95% CI: 0.2, 0.6; P(trend) = 0.0001), whereas other dietary folate sources showed no clear association. Methionine intake and serum homocysteine levels were not associated with oral cancer risk. Subjects with the MTHFR C677T homozygous variant (TT) genotype had a nonsignificantly lower risk, and risk patterns tended to differ by level of folate, methionine, alcohol intake and smoking, although the power to detect significant associations in subgroups of these variables was low. Risks for oral cancer are not folate specific; preventive recommendations for this disease should emphasize the importance of a healthy diet, including substantial intake of fruits
— id: 91560, year: 2002, vol: 132, page: 762, stat: Journal Article,

Family cancer history and susceptibility to oral carcinoma in Puerto Rico
Brown, L M; Gridley, G; Diehl, S R; Winn, D M; Harty, L C; Otero, E B; Fraumeni, J F Jr; Hayes, R B
2001 Oct 15;92(8):2102-2108, Cancer
BACKGROUND: Use of alcohol and tobacco are the major risk factors for cancers of the oral cavity and pharynx in most of the world. A heritable component to oral carcinoma risk also has been suggested, although only limited data are available on familial aggregation of this disease. METHODS: A population-based case-control study of 342 subjects with carcinomas of the oral cavity and pharynx (oral carcinoma) and 521 controls was conducted in Puerto Rico. The relation between family history of carcinomas of the oral cavity, the upper aerodigestive tract (UADT), and other selected sites with risk of oral carcinoma was explored using logistic regression modeling techniques. RESULTS: Risk of oral carcinoma was elevated for subjects reporting a first-degree relative with carcinoma of the oral cavity (odds ratio [OR], 2.5; 95% confidence interval [CI], 0.8-8.0) or any UADT carcinoma (OR, 2.6; 95% CI, 1.4-4.8). The increased risk associated with family history of UADT carcinoma tended to be greatest for subjects with known risk factors (i.e., heavy consumption of alcohol and/or tobacco and infrequent intake of raw fruits and vegetables) and with oral carcinoma diagnoses at ages younger than 65 years. CONCLUSIONS: These findings are consistent with a heritable component to oral carcinoma, although shared lifestyle risk factors may be partially involved
— id: 91558, year: 2001, vol: 92, page: 2102, stat: Journal Article,

Diet and nutrition as risk factors for multiple myeloma among blacks and whites in the United States
Brown, L M; Gridley, G; Pottern, L M; Baris, D; Swanso, C A; Silverman, D T; Hayes, R B; Greenberg, R S; Swanson, G M; Schoenberg, J B; Schwartz, A G; Fraumeni, J F Jr
2001 Feb;12(2):117-125, Cancer causes & control. ccc
OBJECTIVES: To explore whether dietary factors contribute to the risk of multiple myeloma and the two-fold higher incidence among blacks compared to whites in the United States. METHODS: Data from a food-frequency questionnaire were analyzed for 346 white and 193 black subjects with multiple myeloma, and 1086 white and 903 black controls who participated in a population-based case-control study of multiple myeloma in three areas of the United States. RESULTS: Elevated risks were associated with obese vs. normal weight (OR = 1.9, 95% confidence interval (CI) = 1.2-3.1 for whites and OR = 1.5, 95% CI = 0.9-2.4 for blacks), while the frequency of obesity was greater for black than white controls. Reduced risks were related to frequent intake of cruciferous vegetables (OR = 0.7, 95% CI = 0.6-0.99) and fish (OR = 0.7, 95% CI = 0.5-0.9) in both races combined, and to vitamin C supplements in whites (OR = 0.6, 95% CI = 0.5-0.9) and blacks (OR = 0.8, 95% CI = 0.5-1.4), with the frequency of vitamin supplement use being greater for white than black controls. However, frequent intake of vitamin C from food and supplements combined was associated with a protective effect in whites (OR = 0.6, 95% CI = 0.4-0.9), but not blacks (OR = 1.2, 95% CI = 0.8-2.1). CONCLUSIONS: The greater use of vitamin C supplements by whites and the higher frequency of obesity among blacks may explain part of the higher incidence of multiple myeloma among blacks compared to whites in the United States. In addition, the increasing prevalence of obesity may have contributed to the upward trend in the incidence of multiple myeloma during recent decades
— id: 91549, year: 2001, vol: 12, page: 117, stat: Journal Article,

Alcohol and prostate cancer
Dennis, L K; Hayes, R B
2001 ;23(1):110-114, Epidemiologic reviews
— id: 91556, year: 2001, vol: 23, page: 110, stat: Journal Article,

Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash
Garcia-Closas, M; Egan, K M; Abruzzo, J; Newcomb, P A; Titus-Ernstoff, L; Franklin, T; Bender, P K; Beck, J C; Le Marchand, L; Lum, A; Alavanja, M; Hayes, R B; Rutter, J; Buetow, K; Brinton, L A; Rothman, N
2001 Jun;10(6):687-696, Cancer epidemiology biomarkers & prevention
Blood samples are an excellent source of large amounts of genomic DNA. However, alternative sources are often needed in epidemiological studies because of difficulties in obtaining blood samples. This report evaluates the buccal cytobrush and alcohol-containing mouthwash protocols for collecting DNA by mail. Several DNA extraction techniques are also evaluated. The study was conducted in two phases. In phase 1, we compared cytobrush and mouthwash samples collected by mail in two different epidemiological studies: (a) cytobrush samples (n = 120) from a United States case-control study of breast cancer; and (b) mouthwash samples (n = 40) from a prospective cohort of male United States farmers. Findings from phase 1 were confirmed in phase 2, where we randomized cytobrush (n = 28) and mouthwash (n = 25) samples among participants in the breast cancer study to directly compare both collection methods. The median human DNA yield determined by hybridization with a human DNA probe from phenol-chloroform extracts was 1.0 and 1.6 microg/2 brushes for phases 1 and 2, respectively, and 27.5 and 16.6 microg/mouthwash sample for phases 1 and 2, respectively. Most (94-100%) mouthwash extracts contained high molecular weight DNA (>23 kb), in contrast to 55-61% of the brush extracts. PCR success rates for amplification of beta-globin gene fragments (268, 536, and 989 bp) were similar for cytobrush and mouthwash phenol-chloroform extracts (range, 94.4-100%). Also, we obtained high success rates in determining the number of CAG repeats in the androgen receptor gene, characterizing tetranucleotide microsatellites in six gene loci, and screening for mutations in the BRCA1/2 genes in a subset of phenol-chloroform DNA extracts. Relative to DNA extracted by phenol-chloroform from cytobrush samples, DNA extracted by NaOH had lower molecular weight, decreased PCR success rates for most assays performed, and unreliably high spectrophotometer readings for DNA yields. In conclusion, although DNA isolated from either mouthwash or cytobrush samples collected by mail from adults is adequate for a wide range of PCR-based assays, a single mouthwash sample provides substantially larger amounts and higher molecular weight DNA than two cytobrush samples
— id: 91551, year: 2001, vol: 10, page: 687, stat: Journal Article,

Relationship of demographic and clinical factors to free and total prostate-specific antigen
Gelmann, E P; Chia, D; Pinsky, P F; Andriole, G L; Crawford, E D; Reding, D; Hayes, R B; Kramer, B S; Woodrum, D L; Gohagan, J K; Levin, D L
2001 Oct;58(4):561-566, Urology
OBJECTIVES: To characterize the role of demographic and clinical parameters in the measurements of prostate-specific antigen (PSA), free PSA (fPSA), and percent free PSA (%fPSA). ME