Jiyoung Ahn, Ph.D.

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,

Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
Brock, Kaye E; Huang, Wen-Yi; Fraser, David R; Ke, Liang; Tseng, Marilyn; Mason, Rebecca S; Stolzenberg-Solomon, Rachael Z; Freedman, D Michal; Ahn, Jiyoung; Peters, Ulrike; McCarty, Catherine; Hollis, Bruce W; Ziegler, Regina G; Purdue, Mark P; Graubard, Barry I
2011 Aug;106(3):339-344, British journal of nutrition
Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case-control studies of 25(OH)D and 1,25(OH)(2)D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(OH)D were low (< 50 nmol/l) in 29 % and very low (< 37 nmol/l) in 11 % of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10 %, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(OH)D and 1,25(OH)(2)D levels. Caucasians who had 25(OH)D >/= 80 nmol/l were half as likely to have diabetes (OR 0.5 (95 % CI 0.3, 0.9)) compared with those who had 25(OH)D < 37 nmol/l. Those in the highest quartile of 1,25(OH)(2)D (>/= 103 pmol/l) were less than half as likely to have diabetes (OR 0.3 (95 % CI 0.1, 0.7)) than those in the lowest quartile (< 72 pmol/l). In conclusion, the independent associations of 25(OH)D and 1,25(OH)(2)D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies
— id: 141193, year: 2011, vol: 106, page: 339, stat: Journal Article,

Association of the oral microbiome with cigarette smoking and oral cancer
Ganly I.; Yang L.; Morris L.; Palmer F.; Deng H.; Ahn J.
2011 ;47:S52-S52, Oral oncology
Objectives: To determine if cigarette smoking and oral squamous cell carcinoma (OSCC) are associated with an alteration of the oral microbiome, and to determine if the oral microbiome is capable of activating cigarette carcinogens. Methods: Oral wash samples were collected from 9 patients with OSCC and 10 non-cancer controls (including 5 smokers and 5 non-smokers). Bacterial DNA was isolated from each oral wash and then 16S rRNA gene survey performed by 454 pyrosequencing of the V3-5 region to identify bacterial sequences present in oral wash samples. Bacterial sequences present in OSCC patient samples and in control patient samples were then categorized. Also, a mock community, composed of 5 bacterial species found in the oral microbiome, was tested for its ability to metabolize cigarette carcinogens. Results: Samples of the oral microbiome were classified into type I and type II microbiomes, based on taxonomic similarity between samples. The type I microbiome was dominated by Grampositive bacteria whereas the type II microbiome was dominated by Gram-negative bacteria. Non-cancer control patients had the type I microbiome (9/10). In contrast, OSCC patients had the type II microbiome (6/9). Furthermore, OSCC was associated with an apparent decrease in the relative abundance of Streptococcus (22.3%) compared with non-smoking (39.4%) and smoking controls (40.1%). There was a step-wise increase in the relative abundance of Veilonella along the non-smoking controls (2.3%) -> smoking controls (6.8%) -> OSCC (9.9%) sequence. Metabolomic analysis demonstrated that a mock bacterial community composed of Streptococcus mitis and Veilonella dispar was able to hydroxylate N-nitrosodieth-ylamine and degrade p-chloroaniline, both being carcinogens found in cigarette smoke. Conclusions: Cigarette smoking and oral squamous cell carcinoma are associated with an alteration of the oral microbiome. The oral microbiome has the potential to modulate oral cancer risk by activating cigarette carcinogens
— id: 136628, year: 2011, vol: 47, page: S52, stat: Journal Article,

Comparing statistical methods for removing seasonal variation from vitamin D measurements in case-control studies
Zhang, Hong; Ahn, Jiyoung; Yu, Kai
2011 APR ;4(1):85-93, Statistics & its interface
Vitamin D deficiency has been shown to be associated with multiple clinical outcomes, including osteoporosis, multiple sclerosis and colorectal cancer. In studies of vitamin D effect on disease outcome, vitamin D status is usually measured by a serum biomarker, namely 25-hydroxy vitamin D [25(OH)D]. Since the circulating 25(OH)D concentration varies from season to season and not all blood samples are collected at the same time, the disease-vitamin D relationship can be obscured if the seasonal variation is not adjusted properly. In the literature, a two-step procedure is usually adopted, with the vitamin D level adjusted for the seasonal variation being obtained in the first step, and the effect of vitamin D being assessed based on the adjusted vitamin D level at the second step. This two-step method can generate misleading results as the estimation variance arising from the first step is not taken into account in the second step analysis. We consider three alternative procedures that unify the two steps into a single model. We conduct an extensive simulation study to evaluate the performance of these methods and demonstrate their applications in a study of 25(OH)D effect on prostate cancer risk
— id: 129594, year: 2011, vol: 4, page: 85, 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,

The Expression of Prostate Secretory Protein (PSP) and Hepatocyte Nuclear Factor-1 (HNF) in High Grade Prostate Intrepithelial Neoplasia (HGPIN) and Adenocarcinoma of the Prostate
Blutreich, AM; Sasturkar, S; He, T; Nagar, M; Chiriboga, L; Hayes, R; Melamed, J; Ahn, J
2010 FEB ;23(3):180A-180A, Modern pathology
— id: 109934, year: 2010, vol: 23, page: 180A, stat: Journal Article,

The Expression of Prostate Secretory Protein (PSP) and Hepatocyte Nuclear Factor-1 (HNF) in High Grade Prostate Intrepithelial Neoplasia (HGPIN) and Adenocarcinoma of the Prostate
Blutreich, AM; Sasturkar, S; He, T; Nagar, M; Chiriboga, L; Hayes, R; Melamed, J; Ahn, J
2010 FEB ;90(11):180A-180A, Laboratory investigation
— id: 109953, year: 2010, vol: 90, page: 180A, stat: Journal Article,

Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women
Brock, K; Huang, W-Y; Fraser, D R; Ke, L; Tseng, M; Stolzenberg-Solomon, R; Peters, U; Ahn, J; Purdue, M; Mason, R S; McCarty, C; Ziegler, R G; Graubard, B
2010 Jul;121(1-2):462-466, Journal of steroid biochemistry & molecular biology
The aim of this study was to investigate modifiable predictors of vitamin D status in healthy individuals, aged 55-74, and living across the USA. Vitamin D status [serum 25-hydroxyvitamin D (25(OH)D)] was measured along with age and season at blood collection, demographics, anthropometry, physical activity (PA), diet, and other lifestyle factors in 1357 male and 1264 female controls selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Multivariate linear and logistic regression analyses were used to identify associations with vitamin D status. Three%, 29% and 79% of the population had serum 25(OH)D levels<25, <50 and <80 nmol/L, respectively. The major modifiable predictors of low vitamin D status were low vitamin D dietary and supplement intake, body mass index (BMI) >30 kg/m2, physical inactivity (PA) and low milk and calcium supplement intake. In men, 25(OH)D was determined more by milk intake on cereal and in women, by vitamin D and calcium supplement and menopausal hormone therapy (MHT) use. Thus targeting an increase in vigorous activity and vitamin D and calcium intake and decreasing obesity could be public health interventions independent of sun exposure to improve vitamin D status in middle-aged Americans
— id: 133763, year: 2010, vol: 121, page: 462, 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,

Circulating 25-hydroxyvitamin D and risk of kidney cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Gallicchio, Lisa; Moore, Lee E; Stevens, Victoria L; Ahn, Jiyoung; Albanes, Demetrius; Hartmuller, Virginia; Setiawan, V Wendy; Helzlsouer, Kathy J; Yang, Gong; Xiang, Yong-Bing; Shu, Xiao-Ou; Snyder, Kirk; Weinstein, Stephanie J; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Cai, Qiuyin; Campbell, David S; Chen, Yu; Chow, Wong-Ho; Horst, Ronald L; Kolonel, Laurence N; McCullough, Marjorie L; Purdue, Mark P; Koenig, Karen L
2010 Jul 1;172(1):47-57, American journal of epidemiology
Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of > or =75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically
— id: 132233, year: 2010, vol: 172, page: 47, stat: Journal Article,

Transverse myelitis: Retrospective review of 7 cases with different etiologies
Pares N.; Ahn J.; Diaz M.; Gutierrez S.
2010 ;2(9 SUPPL 1):S170-S171, PM&R
Objective: To assess the relationship between etiologyand functional outcome in 7 cases of transverse myelitis after acute inpatient rehabilitation. Design: Retrospective review of 7 cases of transverse myelitis. Setting: Inpatient rehabilitation facility. Participants: One male and 6 female patients, admitted from January 2007 to June 2009, were identified with acute transverse myelitis. Results: Two of the patients were positive for anti-NMO (neuromyelitis optica), one had positive herpes antibody, and the rest were idiopathic. All 7 patients were initially treated with intravenous steroids before admission to our rehabilitation facility. Some of those patients also received IVIG, plasmapheresis, or mitoxantrone. Two patients had multiple recurrences. Their functional outcomes were assessed by using Functional Independence Measure (FIM) score upon admission and at discharge. Discussion: Transverse myelitis is a neurologic condition that affects function of the spinal cord with no history of trauma. Most cases are idiopathic and presumably secondary to autoimmune origin. Multiple diseases can be related to this condition, including NMO, SLE, antiphospholipid antibody syndrome, mixed connective tissue disease, CNS sarcoidosis, and infectious disease (herpes zoster). We reviewed the rehabilitation outcome of patients with acute transverse myelitis by comparing their FIM scores upon admission and at discharge. Conclusions: There is limited literature available that has reported functional outcomes among this population. The patients reviewed on this study had different spinal cord levels of a lesion, and their changes with the FIM score appear to be independent from etiology. There was a significant improvement on the functional status of all the patients after participating on acute inpatient rehabilitation, as per preliminary analysis of the FIM scores on admission and discharge. Successful management of patients with acute transverse myelitis is associated with understanding of its pathophysiology and prevention of secondary complication as well as utilization of all rehabilitation disciplines
— id: 135621, year: 2010, vol: 2, page: S170, 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,

The Expression of Vitamin D Associated Markers in High Grade Prostatic Intraepithelial Neoplasia (HGPIN)
Sasturkar, S; Blutreich, A; He, TW; Nagar, M; Small, J; Chriboga, L; Hayes, R; Melamed, J; Ahn, J
2010 FEB ;23(3):217A-217A, Modern pathology
— id: 109936, year: 2010, vol: 23, page: 217A, stat: Journal Article,

The Expression of Vitamin D Associated Markers in High Grade Prostatic Intraepithelial Neoplasia (HGPIN)
Saturkar, S; Blutreich, A; He, TW; Nagar, M; Small, J; Chiriboga, L; Hayes, R; Melamed, J; Ahn, J
2010 FEB ;90(11):217A-217A, Laboratory investigation
— id: 109955, year: 2010, vol: 90, page: 217A, 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,

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,

Polymorphisms in estrogen- and androgen-metabolizing genes and the risk of gastric cancer
Freedman, Neal D; Ahn, Jiyoung; Hou, Lifang; Lissowska, Jolanta; Zatonski, Witold; Yeager, Meredith; Chanock, Stephen J; Chow, Wong Ho; Abnet, Christian C
2009 Jan;30(1):71-77, Carcinogenesis
Androgens and estrogens may play a role in gastric cancer etiology. To investigate the association of gastric cancer with single-nucleotide polymorphisms (SNPs) in six genes (COMT, CYP1B1, CYP17A1, CYP19A1, HSD17B1 and SHBG) involved in estrogen and androgen synthesis and metabolism, 58 haplotype-tagging SNPs were genotyped in 295 gastric cancer cases and 415 controls from a population-based study in Poland. We assessed differences in haplotype frequency between cases and controls using a global score test and calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for individual haplotypes using logistic regression. We found associations in one linkage disequilibrium (LD) block containing the 3' untranslated region of COMT (rs9332377, rs165728, rs165849 and rs1110478), global score test (df = 4, P = 0.033). Relative to the most frequent GATA haplotype, the GATG haplotype was associated with statistically significant increased gastric cancer risk (OR = 1.50, 95% CI: 1.06-2.12; false discovery rate (FDR) value = 0.459) and the AACA haplotype with borderline increased risk (OR = 1.36, 95% CI = 1.00-1.85; FDR = 0.50). We also found associations for the LD block containing part of the SHBG coding region (rs6258, rs6259, rs2955617, rs1641544 and rs1641537). The CACCC haplotype was associated with statistically significant lower gastric cancer risk relative to the referent CGACC haplotype (OR = 0.55, 95% CI = 0.34-0.90; FDR = 0.459), but the overall score test was statistically non-significant. No other statistically significant associations were observed. In summary, we found possible associations between gastric cancer and polymorphisms in COMT, involved in estrogen inactivation, and SHBG, a modulator of hormone bioavailability. These findings should be interpreted cautiously until replicated in other studies
— id: 98937, year: 2009, vol: 30, page: 71, stat: Journal Article,

Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk
Li, Yulin; Ambrosone, Christine B; McCullough, Marjorie J; Ahn, Jiyoung; Stevens, Victoria L; Thun, Michael J; Hong, Chi-Chen
2009 May;30(5):777-784, Carcinogenesis
Dietary antioxidants may interact with endogenous sources of pro- and antioxidants to impact breast cancer risk. A nested case-control study of postmenopausal women (505 cases and 502 controls) from the Cancer Prevention Study-II Nutrition Cohort was conducted to examine the interaction between oxidative stress-related genes and level of vegetable and fruit intake on breast cancer risk. Genetic variations in catalase (CAT) (C-262T), myeloperoxidase (MPO) (G-463A), endothelial nitric oxide synthase (NOS3) (G894T) and heme oxygenase-1 (HO-1) [(GT)(n) dinucleotide length polymorphism] were not associated with breast cancer risk. Women carrying the low-risk CAT CC [odds ratio (OR) = 0.75, 95% confidence interval (CI) 0.50-1.11], NOS3 TT (OR = 0.54, 95% CI = 0.26-1.12, P-trend = 0.10) or HO-1 S allele and MM genotype (OR = 0.56, 95% CI = 0.37-0.55), however, were found to be at non-significantly reduced breast cancer risk among those with high vegetable and fruit intake (> or = median; P-interactions = 0.04 for CAT, P = 0.005 for NOS3 and P = 0.07 for HO-1). Furthermore, those with > or = 4 putative low-risk alleles in total had significantly reduced risk (OR = 0.53, 95% CI = 0.32-0.88, P-interaction = 0.006) compared with those with < or = 2 low-risk alleles. In contrast, among women with low vegetable and fruit intake (< median), the low-risk CAT CC (OR = 1.33, 95% CI = 0.89-1.99), NOS3 TT (OR = 2.93, 95% CI = 1.38-6.22) and MPO AA (OR = 2.09, 95% CI = 0.73-5.95) genotypes appeared to be associated with raised breast cancer risk, with significantly increased risks observed in those with > or = 4 low-risk alleles compared with participants with < or = 2 low-risk alleles (OR = 1.77, 95% CI = 1.05-2.99, P-interaction = 0.006). Our results support the hypothesis that there are joint effects of endogenous and exogenous antioxidants
— id: 98935, year: 2009, vol: 30, page: 777, stat: Journal Article,

PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk
McCarty, Kathleen M; Santella, Regina M; Steck, Susan E; Cleveland, Rebecca J; Ahn, Jiyoung; Ambrosone, Christine B; North, Kari; Sagiv, Sharon K; Eng, Sybil M; Teitelbaum, Susan L; Neugut, Alfred I; Gammon, Marilie D
2009 Apr;117(4):552-558, Environmental health perspectives
BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker. OBJECTIVE: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoking. METHODS: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973). RESULTS: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively). CONCLUSION: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk
— id: 98932, year: 2009, vol: 117, page: 552, stat: Journal Article,

Adipokine genes and prostate cancer risk
Moore, Steven C; Leitzmann, Michael F; Albanes, Demetrius; Weinstein, Stephanie J; Snyder, Kirk; Virtamo, Jarmo; Ahn, Jiyoung; Mayne, Susan T; Yu, Herbert; Peters, Ulrike; Gunter, Marc J
2009 Feb 15;124(4):869-876, International journal of cancer
Adiposity and adipocyte-derived cytokines have been implicated in prostate carcinogenesis. However, the relationship of adipokine gene variants with prostate cancer risk has not been thoroughly investigated. We therefore examined common variants of the IL6, LEP, LEPR, TNF and ADIPOQ genes in relation to prostate cancer in a case-control study nested within a large cohort of Finnish men. The study sample consisted of 1,053 cases of prostate cancer, diagnosed over an average 11 years of follow up, and 1,053 controls matched to the cases on age, intervention group and date of baseline blood draw. Logistic regression was used to model the relative odds of prostate cancer. We also examined genotypes in relation to serum insulin, IGF-1 and IGF-1:IGFBP-3 among 196 controls. Variant alleles at three loci (-14858A>G, -13973A>C, -13736C>A) in a potential regulatory region of the LEP gene conferred a statistically significant 20% reduced risk of prostate cancer. For example, at the -14858A>G locus, heterozygotes and homozygotes for the A allele had an odds ratio (OR) of prostate cancer of 0.76 [95% confidence interval (CI) 0.62, 0.93] and 0.79 (95% CI 0.60, 1.04), respectively. At 13288G>A, relative to the GG genotype, the AA genotype was associated with a suggestive increased risk of prostate cancer (OR = 1.29; 95% CI 0.99,1.67; p(trend) = 0.05). Polymorphisms in the IL6, LEPR, TNF and ADIPOQ genes were not associated with prostate cancer. Allelic variants in the LEP gene are related to prostate cancer risk, supporting a role for leptin in prostate carcinogenesis
— id: 98936, year: 2009, vol: 124, page: 869, stat: Journal Article,

Age-specific physical activity and prostate cancer risk among white men and black men
Moore, Steven C; Peters, Tricia M; Ahn, Jiyoung; Park, Yikyung; Schatzkin, Arthur; Albanes, Demetrius; Hollenbeck, Albert; Leitzmann, Michael F
2009 Jul 30;115(21):5060-5070, Cancer
BACKGROUND:: The relation of physical activity across the lifespan to risk of prostate cancer has not been thoroughly investigated, particularly among black men. The authors investigated physical activity, including activity during different age periods and of various intensities, in relation to prostate cancer incidence among white men and black men. METHODS:: In total, 160,006 white men and 3671 black men ages 51 years to 72 years who were enrolled in the National Institutes of Health-AARP Diet and Health Study reported their time spent per week engaging in physical activity during ages 15 to 18 years, 19 years to 29 years, 35 years to 39 years, and during the past 10 years. Cox regression models were used to examine physical activity, categorized by intensity (moderate or vigorous, light, and total), in relation to prostate cancer risk. RESULTS:: During 7 years of follow-up, 9624 white men and 371 black men developed prostate cancer. Among white men, physical activity had no association with prostate cancer regardless of age period or activity intensity. Among black men, engaging in >/=4 hours of moderate/vigorous intensity physical activity versus infrequent activity during ages 19 years to 29 years was related to a 35% lower risk of prostate cancer (relative risk, 0.65; 95% confidence interval [95% CI], 0.43-0.99 [P(trend) = .01]). Frequent moderate/vigorous physical activity at ages 35 years to 39 years also potentially was related to reduced prostate cancer risk (relative risk, 0.59; 95% CI, 0.36-0.96 [P(trend) = .15]). CONCLUSIONS:: Regular physical activity may reduce prostate cancer risk among black men, and activity during young adulthood may yield the greatest benefit. This novel finding needs confirmation in additional studies. Cancer 2009. Published 2009 by the American Cancer Society
— id: 101336, year: 2009, vol: 115, page: 5060, 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,

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,

Family history of prostate cancer and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
Ahn, Jiyoung; Moslehi, Roxana; Weinstein, Stephanie J; Snyder, Kirk; Virtamo, Jarmo; Albanes, Demetrius
2008 Sep 1;123(5):1154-1159, International journal of cancer
Prostate cancer family history has been associated with increased risk of the malignancy. Most prior studies have been retrospective and subject to recall bias, however, and data evaluating interactions with other important risk factors are limited. We examined the relationship between a family history of prostate cancer and prostate cancer risk in relation to body size, micronutrients and other exposures in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of Finnish male smokers. Family history of cancer information was self-reported once during the study in 1991, and anthropometry was measured by trained personnel. Among 19,652 men with complete data, 1,111 incident cases were identified during up to 12.3 years of follow-up. A first-degree family history of prostate cancer was associated with an overall relative risk (RR) of 1.91 (95% CI = 1.49-2.47) and a RR of 4.16 (95% CI = 2.67-6.49) for advanced disease (stage >or= 3), adjusted for age and trial intervention. Our data also suggest that to some degree, height, body mass index, and serum alpha-tocopherol and beta-carotene modify the family history and prostate cancer association, although the interactions were not statistically significant. Supplementation with vitamin E or beta-carotene did not modify the family history-prostate cancer association. This study provides additional evidence that family history is a significant risk factor for prostate cancer
— id: 98940, year: 2008, vol: 123, page: 1154, 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,

Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Leitzmann, Michael F; Ahn, Jiyoung; Albanes, Demetrius; Hsing, Ann W; Schatzkin, Arthur; Chang, Shih-Chen; Huang, Wen-Yi; Weiss, Jocelyn M; Danforth, Kim N; Grubb, Robert L 3rd; Andriole, Gerald L
2008 Dec;19(10):1267-1276, Cancer causes & control. ccc
OBJECTIVE: A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism. METHODS: We prospectively examined the diabetes-prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. RESULTS: During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68-0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62-0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum >or=8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2)) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively). CONCLUSION: In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI
— id: 98939, year: 2008, vol: 19, page: 1267, stat: Journal Article,

Physical activity in relation to total, advanced, and fatal prostate cancer
Moore, Steven C; Peters, Tricia M; Ahn, Jiyoung; Park, Yikyung; Schatzkin, Arthur; Albanes, Demetrius; Ballard-Barbash, Rachel; Hollenbeck, Albert; Leitzmann, Michael F
2008 Sep;17(9):2458-2466, Cancer epidemiology biomarkers & prevention
Physical activity has been inconsistently related to total prostate cancer and few studies have examined whether this association varies by disease aggressiveness. We examined physical activity in relation to total, advanced, and fatal prostate cancer in the NIH-AARP Diet and Health Study. At baseline (1995-1996), 293,902 men ages 50 to 71 years completed a questionnaire inquiring about current frequency of vigorous exercise of at least 20 min of duration, as well as frequency of exercise during adolescence (ages 15-18). We used proportional hazards regression to calculate multivariate relative risks (RR) and 95% confidence intervals (95% CI). During up to 8.2 years of follow-up, 17,872 prostate cancer cases were identified, including 1,942 advanced and 513 fatal cases. Comparing frequent (5+ times per week) versus infrequent (less than once per week) vigorous exercise, exercise at baseline was not associated with risk of total prostate cancer (RR, 1.01; 95% CI, 0.96-1.07; P(trend) = 0.78), advanced prostate cancer (RR, 1.14; 95% CI, 0.97-1.33; P(trend) = 0.25), or fatal prostate cancer (RR, 0.90; 95% CI, 0.67-1.20; P(trend) = 0.12). Increasing level of vigorous exercise during adolescence was associated with a small 3% reduction in total prostate cancer risk (frequent versus infrequent exercise during adolescence: RR, 0.97; 95% CI, 0.91-1.03; P(trend) = 0.03) but was not associated with risk of advanced prostate cancer (RR, 0.95; 95% CI, 0.78-1.14; P(trend) = 0.18) or fatal prostate cancer (RR, 0.96; 95% CI, 0.67-1.36; P(trend) = 0.99). Neither vigorous exercise at baseline nor exercise during adolescence was related to risk of total, advanced, or fatal prostate cancer in this large prospective cohort
— id: 98938, year: 2008, vol: 17, page: 2458, 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,

Adiposity, adult weight change, and postmenopausal breast cancer risk
Ahn, Jiyoung; Schatzkin, Arthur; Lacey, James V Jr; Albanes, Demetrius; Ballard-Barbash, Rachel; Adams, Kenneth F; Kipnis, Victor; Mouw, Traci; Hollenbeck, Albert R; Leitzmann, Michael F
2007 Oct 22;167(19):2091-2102, Archives of internal medicine
BACKGROUND: Obesity is a risk factor for postmenopausal breast cancer, but the role of the timing and amount of adult weight change in breast cancer risk is unclear. METHODS: We prospectively examined the relations of adiposity and adult weight change to breast cancer risk among 99 039 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. Anthropometry was assessed by self-report in 1996. Through 2000, 2111 incident breast cancer cases were ascertained. RESULTS: Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at ages 50 and 35 years, and waist-hip ratio were associated with increased breast cancer risk, particularly in women not using menopausal hormone therapy (MHT). Weight gained between age 18 years and the current age, between ages 18 and 35 years, between ages 35 and 50 years, and between age 50 years and the current age was consistently associated with increased breast cancer risk in MHT nonusers (relative risk [RR], 2.15; 95% confidence interval [CI], 1.35-3.42 for a >/=50-kg weight gain between age 18 years and the current age vs stable weight) but not in current MHT users. Risk associated with adult weight change was stronger in women with later vs earlier age at menarche (RR, 4.20; 95% CI, 2.05-8.64 for >/=15 years vs RR, 1.51; 95% CI, 1.11-2.06 for 11-12 years; P = .007 for interaction). In MHT nonusers, the associations with current BMI and adult weight change were stronger for advanced disease than for nonadvanced disease (P = .009 [current BMI] and .21 [weight gain] for heterogeneity) and were stronger for hormone receptor-positive than hormone receptor-negative tumors (P < .001 for heterogeneity). CONCLUSION: Weight gain throughout adulthood is associated with increased postmenopausal breast cancer risk in MHT nonusers
— id: 98941, year: 2007, vol: 167, page: 2091, stat: Journal Article,

Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer
Hong, Chi-Chen; Ambrosone, Christine B; Ahn, Jiyoung; Choi, Ji-Yeob; McCullough, Marjorie L; Stevens, Victoria L; Rodriguez, Carmen; Thun, Michael J; Calle, Eugenia E
2007 Sep;16(9):1784-1794, Cancer epidemiology biomarkers & prevention
Oxidative stress resulting from excess reactive oxygen species and/or deficiencies in antioxidant capabilities may play a role in breast cancer etiology. In a nested case-control study of postmenopausal women (505 cases and 502 controls) from the American Cancer Society Prevention II Nutrition Cohort, we examined relationships between breast cancer risk and genetic polymorphisms of enzymes involved in the generation and removal of iron-mediated reactive oxygen species. Using unconditional logistic regression, genetic variations in Nrf2 (11108C>T), NQO1 (609C>T), NOS3 (894G>T), and HO-1 [(GT)(n) dinucleotide length polymorphism] were not associated with breast cancer risk in a multivariate model. A significant dose trend (P trend = 0.04), however, was observed for total number of putative 'at-risk' alleles (Nrf T, NQO1 T, NOS T, and HO-1 LL and LM genotypes), with those carrying three or more at-risk alleles having an odds ratio (OR) of 1.56 [95% confidence interval (95% CI), 0.97-2.51] compared with those having none. When examined in relation to iron, carriage of three or more high-risk alleles in the highest tertile of iron intake (OR, 2.27; 95% CI, 0.97-5.29; P trend = 0.02; P interaction = 0.30) or among users of supplemental iron (OR, 2.39; 95% CI, 1.09-5.26; P trend = 0.02; P interaction = 0.11) resulted in a greater than 2-fold increased risk compared with women with no high-risk alleles. Increased risk was also observed among supplement users with the HO-1 LL or LM genotypes (OR, 1.56; 95% CI, 1.01-2.41; P interaction = 0.32) compared with S allele carriers and MM genotypes combined. These results indicate that women with genotypes resulting in potentially higher levels of iron-generated oxidative stress may be at increased risk of breast cancer and that this association may be most relevant among women with high iron intake
— id: 98942, year: 2007, vol: 16, page: 1784, stat: Journal Article,

Alcohol consumption and fatty acid intakes in the 2001-2002 National Health and Nutrition Examination Survey
Kim, Soo Yeon; Breslow, Rosalind A; Ahn, Jiyoung; Salem, Norman Jr
2007 Aug;31(8):1407-1414, Alcoholism: clinical & experimental research
BACKGROUND: Alcohol consumption has the potential to affect dietary intakes of nutrients; however, little is known about fatty acid intakes among alcohol consumers in the U.S. population. METHOD: We examined the relation between self-reported alcohol consumption and dietary fatty acid intake in 4,168 adults in the cross-sectional National Health and Nutrition Examination Survey 2001-2002. Fatty acid intake was determined from a single, interviewer-administered 24-hour recall. The adjusted, weighted mean level of dietary fatty acid intakes, as characterized by nutrient density, was calculated as grams of fatty acid per 1,000 kcal of energy consumed according to average daily alcohol consumption and binge-drinking episodes. RESULTS: Energy intake showed a significant increasing trend across alcohol consumption categories in both genders and binge-drinking categories in men. Women binge drinkers also showed a higher energy intake compared with nonbinge drinkers. Among men, decreased nutrient densities of saturated, monounsaturated, polyunsaturated, linoleic, and alpha-linolenic acids were associated with increasing alcohol consumption. Binge-drinking men but not women had significantly decreased intakes of total saturates, monounsaturates, polyunsaturates and linoleic, alpha-linolenic, eicosapentaenoic, and docosahexaenoic acid. When alcohol energy was excluded from calculation of nutrient densities, the results were similar to those with alcohol energy included, except that total saturated and monounsaturated fatty acid differences were no longer significant. In addition, there was an inverse relationship among men between binge-drinking frequency and total polyunsaturates, linoleic, alpha-linolenic, and eicosapentaenoic acids. CONCLUSION: Our cross-sectional results suggest that alcohol consumption may impact the dietary intake of essential fatty acids (EFAs). Given the public health importance of both alcohol consumption and intakes of EFAs, prospective studies of the relation should be considered
— id: 98943, year: 2007, vol: 31, page: 1407, stat: Journal Article,

Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer
Yang, Jun; Ambrosone, Christine B; Hong, Chi-Chen; Ahn, Jiyoung; Rodriguez, Carmen; Thun, Michael J; Calle, Eugenia E
2007 Jun;28(6):1247-1253, Carcinogenesis
NOS3 and MPO genes encode endothelial nitric oxide synthase and myeloperoxidase (MPO), respectively, which generate nitric oxide and reactive oxygen species. Because cigarette smoking generates reactive species, we hypothesized that NOS3 and MPO polymorphisms could influence susceptibility to breast cancer, particularly among smokers. We examined the associations between NOS3 Glu298Asp and MPO G-463A polymorphisms and breast cancer risk by cigarette smoking among post-menopausal women in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. Included in this analysis were 502 women who provided blood samples and were diagnosed with breast cancer between 1992 and 2001 and 505 cancer-free controls who were matched to the cases by age, race/ethnicity and date of blood donation. Genotyping for NOS3 and MPO was performed using TaqMan, and unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). No statistically significant relationships were found between NOS3 and MPO genotypes and breast cancer risk. When considering smoking, variant NOS3 genotypes (GT and TT) were significantly associated with reduced breast cancer risk among never smokers (OR = 0.67, 95% CI = 0.45-0.99), but were associated with higher risk among ever smokers (OR = 1.59, 95% CI = 1.05-2.41) and 2-fold increase in risk for those who smoked >10 cigarettes per day (OR = 2.19, 95% CI = 1.21-3.97). NOS3 genotypes appeared to be associated with risk of post-menopausal breast cancer among smokers, supporting the hypothesis that subgroups of women based upon genetic profiles may be at higher risk of breast cancer when exposed to tobacco smoke
— id: 98944, year: 2007, vol: 28, page: 1247, stat: Journal Article,

Oxidative stress and breast cancer
Ahn J; Ambrosone CB
Oxidative stress, disease and cancer London : Imperial College Press, 2006,
— id: 5204, year: 2006, vol: , page: ?, stat: Chapter,

Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer
Ahn, Jiyoung; Ambrosone, Christine B; Kanetsky, Peter A; Tian, Chunqiao; Lehman, Teresa A; Kropp, Silke; Helmbold, Irmgard; von Fournier, Dietrich; Haase, Wulf; Sautter-Bihl, Marie Luise; Wenz, Frederik; Chang-Claude, Jenny
2006 Dec 1;12(23):7063-7070, Clinical cancer research
PURPOSE: Because radiotherapy exerts cytotoxic effects via generation of massive oxidative stress, we hypothesized that catalase, manganese superoxide dismutase, myeloperoxidase (MPO), and endothelial nitric oxide synthase (eNOS) genotypes might result in greater risk of radiotoxicity. EXPERIMENTAL DESIGN: Cases (n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. The development of acute reactions (moist desquamation) associated with genotypes was modeled using the Cox proportional hazards model, accounting for cumulative biologically effective radiation dose. RESULTS: Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity. However, relationships between overweight/obesity [body mass index (BMI), >25] and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Women with high BMI (>25) and eNOS GG genotypes were at more than a 6-fold increase in risk (hazard ratio, 6.39; 95% confidence interval, 2.53-16.15) compared with those with BMI <25, and for MPO, those with high BMI (>25) and GG genotypes also had greater risk of radiotoxicity (hazard ratio, 3.61; 95% confidence interval, 1.78-7.35) compared with those with BMI <25. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. Exploratory analysis using classification and regression trees indicated that total number of risk alleles contributed, in part, to acute toxicity outcomes among a subgroup of women. CONCLUSIONS: Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment
— id: 98945, year: 2006, vol: 12, page: 7063, stat: Journal Article,

Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers on breast cancer risk
Ahn, Jiyoung; Gammon, Marilie D; Santella, Regina M; Gaudet, Mia M; Britton, Julie A; Teitelbaum, Susan L; Terry, Mary Beth; Neugut, Alfred I; Eng, Sybil M; Zhang, Yuesheng; Garza, Cutberto; Ambrosone, Christine B
2006 Sep;27(9):1876-1882, Carcinogenesis
Glutathione S-transferases (GSTs) are phase II enzymes that are involved in the detoxification of a wide range of carcinogens. The novel GSTA1*A and GSTA1*B genetic polymorphism results in differential expression, with lower transcriptional activation of GSTA1*B (variant) than that of GSTA1*A (common) allele. Considering that cruciferous vegetables induce GSTs, which metabolize tobacco smoke carcinogens, we hypothesized that the variant GSTA1*B genotype may predispose women to breast cancer, particularly among low cruciferous vegetable consumers and among smokers. Thus, we evaluated potential relationships between GSTA1 polymorphisms and breast cancer risk, in relation to vegetable consumption and smoking status in the Long Island Breast Cancer Study Project (1996-1997), a population-based case-control study. Genotyping (1036 cases and 1089 controls) was performed, and putative breast cancer risk factors and usual dietary intakes were assessed. Having GSTA1*A/*B or *B/*B genotypes was not associated with increased breast cancer risk, compared to having the common *A/*A genotype. However, among women in the lowest two tertiles of cruciferous vegetable consumption, *B/*B genotypes were associated with increased risk (OR (95% CI)=1.73 (1.10-2.72) for 0-1 servings/week), compared to women with *A/*A genotypes. Among women with *B/*B genotypes, a significant inverse trend between cruciferous vegetable consumption and breast cancer risk was observed (P for trend=0.05), and higher consumption (4+ servings/week) ameliorated the increased risk associated with the genotype. Current smokers with *B/*B genotypes had a 1.89-fold increase in risk (OR (95% CI)=1.89 (1.09-3.25)), compared with never smokers with *A/*A genotypes. These data indicate that GSTA1 genotypes related to reduced GSTA1 expression are associated with increased breast cancer primarily among women with lower consumption of cruciferous vegetables and among current smokers
— id: 100209, year: 2006, vol: 27, page: 1876, stat: Journal Article,

Associations between catalase phenotype and genotype: modification by epidemiologic factors
Ahn, Jiyoung; Nowell, Susan; McCann, Susan E; Yu, Jihnhee; Carter, Lisa; Lang, Nicholas P; Kadlubar, Fred F; Ratnasinghe, Luke D; Ambrosone, Christine B
2006 Jun;15(6):1217-1222, Cancer epidemiology biomarkers & prevention
Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide and is induced by oxidative challenge. A -262C --> T polymorphism in the promoter region of the gene (CAT) is associated with risk of several conditions related to oxidative stress. We sought to determine the functional effects of the CAT polymorphism on enzyme activity in erythrocytes and the potential modifying effects of demographic and lifestyle factors on genotype/phenotype relationships, using specimens and data from controls from breast and prostate cancer studies in Arkansas (n = 420). There was a dose-response reduction in catalase activity by genotype, with geometric means of 115.4 units/mg hemoglobin for those with CC genotypes, 82.1 units/mg for those with CT genotypes, and 73.5 units/mg for those with TT genotypes. Associations were only observed among Caucasians (P < 0.0001), with no effects among African Americans (P = 0.91), and were stronger among women than men, although numbers in stratified analyses were small. Differences in catalase activity by genotype were most pronounced among those in the highest tertiles of consumption of fruits and vegetables (-35%, P = 0.003), with weaker relationships among those who were lower consumers (-21.8%, P = 0.16). Among those with CC genotypes, there was no change in activity by consumption, but there were notable decreases in activity by tertiles of consumption for those with at least one T allele. These data indicate that the CAT -262C --> T polymorphism predicts a portion of catalase phenotype, which may be limited to Caucasians. Associations between genotype and phenotype were modified by dietary factors, illustrating the biochemical complexity of studies of genetic polymorphisms and disease risk
— id: 100208, year: 2006, vol: 15, page: 1217, stat: Journal Article,

No association between serum insulin-like growth factor (IGF)-I, IGF-binding protein-3, and lung cancer risk
Ahn, Jiyoung; Weinstein, Stephanie J; Snyder, Kirk; Pollak, Michael N; Virtamo, Jarmo; Albanes, Demetrius
2006 Oct;15(10):2010-2012, Cancer epidemiology biomarkers & prevention
— id: 98946, year: 2006, vol: 15, page: 2010, stat: Journal Article,

Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: a case-series study
Ambrosone, Christine B; Tian, Chunqiao; Ahn, Jiyoung; Kropp, Silke; Helmbold, Irmgard; von Fournier, Dietrich; Haase, Wulf; Sautter-Bihl, Marie Luise; Wenz, Frederik; Chang-Claude, Jenny
2006 ;8(4):R40-R40, Breast cancer research
INTRODUCTION: The cytotoxic effects of radiation therapy are mediated primarily through increased formation of hydroxyl radicals and reactive oxygen species, which can damage cells, proteins and DNA; the glutathione S-transferases (GSTs) function to protect against oxidative stress. We hypothesized that polymorphisms encoding reduced or absent activity in the GSTs might result in greater risk for radiation-associated toxicity. METHODS: Women receiving therapy in radiation units in Germany following lumpectomy for breast cancer (1998-2001) provided a blood sample and completed an epidemiological questionnaire (n = 446). Genotypes were determined using Sequonom MALDI-TOF (GSTA1, GSTP1) and Masscode (GSTM1, GSTT1). Biologically effective radiotherapy dose (BED) was calculated, accounting for differences in fractionation and overall treatment time. Side effects considered were grade 2c and above, as classified using the modified Common Toxicity Criteria. Predictors of toxicity were modelled using Cox regression models in relation to BED, with adjustment for treating clinic, photon field, beam energy and boost method, and potential confounding variables. RESULTS: Low activity GSTP1 genotypes were associated with a greater than twofold increase in risk for acute skin toxicities (adjusted hazard ratio 2.28, 95% confidence interval 1.04-4.99). No associations were noted for the other GST genotypes. CONCLUSION: These data indicate that GSTP1 plays an important role in protecting normal cells from damage associated with radiation therapy. Studies examining the effects of GSTP1 polymorphisms on toxicity, recurrence and survival will further inform individualized therapeutics based on genotypes
— id: 100207, year: 2006, vol: 8, page: R40, stat: Journal Article,

Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival
Martin, Robert C G; Ahn, Jiyoung; Nowell, Susan A; Hein, David W; Doll, Mark A; Martini, Benjamin D; Ambrosone, Christine B
2006 ;8(4):R45-R45, Breast cancer research
BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk and survival in breast cancer. This base pair transition (-9 T > C) leads to a valine to alanine amino acid change in the mitochondrial targeting sequence. A polymorphism has also been identified in the proximal region of the promoter (-102 C>T) that alters the recognition sequence of the AP-2 transcription factor, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the -102 C>T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study. MATERIALS AND METHODS: The relationship between the MnSOD -102 C>T polymorphism and survival was examined in a cohort of 291 women who received chemotherapy and/or radiotherapy for incident breast cancer. The MnSOD -102 C>T genotype was determined using a TaqMan allele discrimination assay. Patient survival was evaluated according to the MnSOD genotype using Kaplan-Meier survival functions. Hazard ratios were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. RESULTS: In an evaluation of all women, there was a borderline significant reduction in recurrence-free survival with either one or both variant alleles (CT + TT) when compared with patients with wild-type alleles (CC) (odds ratio, 0.65; 95% confidence interval, 0.42-1.01). When the analysis was restricted to patients receiving radiation therapy, there was a significant reduction in relapse-free survival in women who were heterozygous for the MnSOD -102 genotype (relative risk, 0.40; 95% confidence interval, 0.18-0.86). Similarly, when the homozygous and heterozygous variant genotypes were combined, there remained a significant reduction in relapse-free survival in this group (hazard ratio, 0.42; 95% confidence interval, 0.20-0.87). CONCLUSION: The MnSOD -102 variant allele appears to be associated with an improved recurrence-free survival in all patients, and more dramatically in subjects who received adjuvant radiation therapy
— id: 98947, year: 2006, vol: 8, page: R45, stat: Journal Article,

No association between glutathione peroxidase Pro198Leu polymorphism and breast cancer risk
Ahn, Jiyoung; Gammon, Marilie D; Santella, Regina M; Gaudet, Mia M; Britton, Julie A; Teitelbaum, Susan L; Terry, Mary Beth; Neugut, Alfred I; Ambrosone, Christine B
2005 Oct;14(10):2459-2461, Cancer epidemiology biomarkers & prevention
— id: 98949, year: 2005, vol: 14, page: 2459, stat: Journal Article,

Associations between breast cancer risk and the catalase genotype, fruit and vegetable consumption, and supplement use
Ahn, Jiyoung; Gammon, Marilie D; Santella, Regina M; Gaudet, Mia M; Britton, Julie A; Teitelbaum, Susan L; Terry, Mary Beth; Nowell, Susan; Davis, Warren; Garza, Cutberto; Neugut, Alfred I; Ambrosone, Christine B
2005 Nov 15;162(10):943-952, American journal of epidemiology
Observed weak or null associations between fruit and vegetable intake and breast cancer risk could be due to heterogeneity in endogenous antioxidant capabilities. The authors evaluated potential relations between a functional polymorphism in catalase, an antioxidant enzyme, and breast cancer risk, particularly in relation to fruit and vegetable intake and supplement use. Women (1,008 cases and 1,056 controls) in the Long Island Breast Cancer Study Project (1996-1997) were interviewed, completed a food frequency questionnaire, and provided blood for genotyping. The high-activity catalase CC genotype was associated with an overall 17% reduction in risk of breast cancer compared with having at least one variant T allele (odds ratio = 0.83, 95% confidence interval: 0.69, 1.00). Vegetable and, particularly, fruit consumption contributed to the decreased risk associated with the catalase CC genotype. Associations were more pronounced among women who did not use vitamin supplements, with a significant multiplicative interaction (p(interaction) = 0.02) for the CC genotype and high fruit intake (odds ratio = 0.59, 95% confidence interval: 0.38, 0.89), and there was no association among supplement users. These results indicate the importance of diet, rather than supplement use, in concert with endogenous antioxidant capabilities, in the reduction of breast cancer risk. CC genotypes were prevalent in approximately 64% of controls; thus, the preventive potential for fruit consumption has widespread implications
— id: 98950, year: 2005, vol: 162, page: 943, stat: Journal Article,

Antioxidant supplements, genetics, and chemotherapy outcomes
Ambrosone CB; Ahn J; Schoenenberger V
2005 ;1(3):251-258, Current Cancer Therapy Reviews
— id: 100212, year: 2005, vol: 1, page: 251, stat: Journal Article,

Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer
Ambrosone, Christine B; Ahn, Jiyoung; Singh, Keshav K; Rezaishiraz, Hamed; Furberg, Helena; Sweeney, Carol; Coles, Brian; Trovato, Andrew
2005 Feb 1;65(3):1105-1111, Cancer research
The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer
— id: 98952, year: 2005, vol: 65, page: 1105, stat: Journal Article,

Association of genetic variation in tamoxifen-metabolizing enzymes with overall survival and recurrence of disease in breast cancer patients
Nowell, Susan A; Ahn, Jiyoung; Rae, James M; Scheys, Joshua O; Trovato, Andrew; Sweeney, Carol; MacLeod, Stewart L; Kadlubar, Fred F; Ambrosone, Christine B
2005 Jun;91(3):249-258, Breast cancer research & treatment
Tamoxifen has been a mainstay of adjuvant therapy for breast cancer for many years. We sought to determine if genetic variability in the tamoxifen metabolic pathway influenced overall survival in breast cancer patients treated with tamoxifen. We examined functional polymorphisms in CYP2D6, the P450 catalyzing the formation of active tamoxifen metabolites, and UGT2B15, a Phase II enzyme facilitating the elimination of active metabolite in a retrospective study of breast cancer patients. We also examined whether the combination of variant alleles in SULT1A1 and UGT2B15 had more of an impact on overall survival in tamoxifen-treated patients than when the genes were examined separately. We conducted a retrospective study using archived paraffin blocks for DNA extraction and data from pathology reports and hospital tumor registry data for information on clinical characteristics, treatment, and outcomes (162 patients receiving tamoxifen and 175 who did not). Genotypes for CYP2D6 and UGT2B15 were obtained and Cox proportional hazards modeling was performed. After adjusting for age, race, stage of disease at diagnosis, and hormone receptor status, we found no significant association between CYP2D6 genotype and overall survival in either group of breast cancer patients. Tamoxifen-treated patients with UGT2B15 high activity genotypes had increased risk of recurrence and poorer survival. When UGT2B15 and SULT1A1 'at-risk' alleles were combined, women with two variant alleles had significantly greater risk of recurrence and poorer survival than those with common alleles. These studies indicate that genetic variation in Phase II conjugating enzymes can influence the efficacy of tamoxifen therapy for breast cancer
— id: 98951, year: 2005, vol: 91, page: 249, stat: Journal Article,

Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer
Sato, Eiichi; Olson, Sara H; Ahn, Jiyoung; Bundy, Brian; Nishikawa, Hiroyoshi; Qian, Feng; Jungbluth, Achim A; Frosina, Denise; Gnjatic, Sacha; Ambrosone, Christine; Kepner, James; Odunsi, Tosin; Ritter, Gerd; Lele, Shashikant; Chen, Yao-Tseng; Ohtani, Haruo; Old, Lloyd J; Odunsi, Kunle
2005 Dec 20;102(51):18538-18543, Proceedings of the National Academy of Sciences of the United States of America
In a recent report, [Zhang et al. (2003) N. Engl. J. Med. 348, 203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; P = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-ESO-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer
— id: 98948, year: 2005, vol: 102, page: 18538, stat: Journal Article,

Myeloperoxidase genotype, fruit and vegetable consumption, and breast cancer risk
Ahn, Jiyoung; Gammon, Marilie D; Santella, Regina M; Gaudet, Mia M; Britton, Julie A; Teitelbaum, Susan L; Terry, Mary Beth; Neugut, Alfred I; Josephy, P David; Ambrosone, Christine B
2004 Oct 15;64(20):7634-7639, Cancer research
Myeloperoxidase (MPO), an antimicrobial enzyme in the breast, generates reactive oxygen species (ROS) endogenously. An MPO G463A polymorphism exists in the promoter region, with the variant A allele conferring lower transcription activity than the common G allele. Because oxidative stress may play a role in breast carcinogenesis, we evaluated MPO genotypes in relation to breast cancer risk among 1,011 cases and 1,067 controls from the Long Island Breast Cancer Study Project (1996-1997). We also assessed the potential modifying effects of dietary antioxidants and hormonally related risk factors on these relationships. Women over 20 years with incident breast cancer who were residents of Nassau and Suffolk Counties, NY, were identified as potential cases. Population-based controls were frequency matched by 5-year age groups. Genotyping was performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) technology, and suspected breast cancer risk factors and usual dietary intake were assessed during an in-person interview. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Having at least one A allele was associated with an overall 13% reduction in breast cancer risk. When consumption of fruits and vegetables and specific dietary antioxidants were dichotomized at the median, inverse associations with either GA or AA genotypes were most pronounced among women who consumed higher amounts of total fruits and vegetables (odds ratio, 0.75; 95% confidence interval, 0.58-0.97); this association was not noted among the low-consumption group (P for interaction = 0.04). Relationships were strongest among premenopausal women. Results from this first study of MPO genotypes and breast cancer risk indicate that MPO variants, related to reduced generation of ROS, are associated with decreased breast cancer risk, and emphasize the importance of fruit and vegetable consumption in reduction of breast cancer risk
— id: 98954, year: 2004, vol: 64, page: 7634, stat: Journal Article,

Gene-nutrient interactions in cancer etiology
Nowell, Susan A; Ahn, Jiyoung; Ambrosone, Christine B
2004 Nov;62(11):427-438, Nutrition reviews
Relationships between dietary components and cancer risk are often unclear, and the results from epidemiologic studies are inconsistent. While some inconsistencies could be due to study design issues, we propose that genetic heterogeneity of study populations could mask associations. In this report, we review the literature regarding meat consumption and risk of colon, breast, and prostate cancers, particularly in relation to phenotypes and genotypes for enzymes that metabolize food-borne promutagens. The role of consumption of fruits and vegetables, as well as the role of genetic variants in oxidative stress genes, in the risk of breast cancer are also discussed
— id: 98953, year: 2004, vol: 62, page: 427, stat: Journal Article,

Effects of soy protein concentrate and age on plasma lipids and phospholipid fatty acid patterns in female rats
Chung EJ; Kim SY; Kim JY; Ahn J; Park JW; Cha MH; Lee-Kim YC
2003 ;32(2):269-277, Han'guk Sikp'um Yongyang Kwahakhoe chi = Journal of the Korean Society of Food Science & Nutrition
— id: 100211, year: 2003, vol: 32, page: 269, stat: Journal Article,

Fatty acid patterns in gastric mucosa of stomach cancer patients
Ahn, J; Park, I S; Lee, K S; Kim, S Y; Chung, E J; Kim, J; Kim, D J; Yoon, S; Lee-Kim, Y C
2001 Apr;42(2):220-226, Yonsei medical journal
omega6 and omega3 fatty acids are important cellular components and known to be involved in disease processes. However, few studies have focused on mucosa fatty acid in human gastric cancer. The purpose of this study was to investigate how fatty acid patterns of mucosa are altered in gastric cancer. Fatty acids were analyzed by gas chromatography and their relative compositions (%) were determined and evaluated both in mucosa total-fatty acids and in phospholipid-fatty acids in paired cancerous and non-cancerous gastric cancer tissues (n = 18). The level of arachidonic acid (20:4omega6, AA) appeared significantly higher both in phospholipid-fatty acids (p < 0.05) and in total-fatty acids (p < 0.001) in cancerous mucosa compared to non-cancerous mucosa. The omega6/omega3 fatty acid ratio of phospholipid-fatty acids was also significantly higher in cancerous mucosa. The higher level of AA in cancerous tissue can be partially explained by the higher ratio of 20:4omega 6/20:3omega6 (desaturation index) and the lower ratio of 22:4omega6/20:4 omega6 (elongation index). The change in the relative composition of arachidonic acid may influence the production of prostaglandins and related metabolites, which regulate cell differentiation and proliferation. The findings of this study with respect to fatty acid changes, especially in terms of arachidonic acid metabolism, may be of relevance in the understanding of the roles of specific fatty acids and possibly of eicosanoids in gastric cancer
— id: 100210, year: 2001, vol: 42, page: 220, stat: Journal Article,