Paolo G Toniolo, M.D.

Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer
Lukanova, Annekatrin; Surcel, Helja-Marja; Lundin, Eva; Kaasila, Marjo; Lakso, Hans-Ake; Schock, Helena; Husing, Anika; Kaaks, Rudolf; Koskela, Pentti; Grankvist, Kjell; Pukkala, Eero; Zeleniuch-Jacquotte, Anne; Lehtinen, Matti; Toniolo, Paolo
2012 Feb 15;130(4):910-920, International journal of cancer
Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (+/-6 months) and date of sampling (+/-3 months) were selected. Estradiol, estrone and progesterone in first-trimester serum were measured by high-performance liquid chromatography tandem mass spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08-3.06), but inversely associated with risk in women who were diagnosed >/=age 40 (upper quartile OR, 0.64; CI, 0.40-1.04), p(interaction) 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40
— id: 149791, year: 2012, vol: 130, page: 910, stat: Journal Article,

Determinants of Maternal Sex Steroids During the First Half of Pregnancy (vol 118, pg 1029, 2011)
Toriola, A. T.; Vaarasmaki, M.; Lehtinen, M.; Zeleniuch-Jacquotte, A.; Lundin, E.; Rodgers, K-G; Lakso, H-A; Chen, T.; Schock, H.; Hallmans, G.; Pukkala, E.; Toniolo, P.; Grankvist, K.; Surcel, H-M; Lukanova, A.
2012 JAN ;119(1):186-187, Obstetrics & gynecology
— id: 150250, year: 2012, vol: 119, page: 186, stat: Journal Article,

Characterization of a genomic signature of pregnancy identified in the breast
Belitskaya-Levy, Ilana; Zeleniuch-Jacquotte, Anne; Russo, Jose; Russo, Irma H; Bordas, Pal; Ahman, Janet; Afanasyeva, Yelena; Johansson, Robert; Lenner, Per; Li, Xiaochun; de Cicco, Ricardo Lopez; Peri, Suraj; Ross, Eric; Russo, Patricia A; Santucci-Pereira, Julia; Sheriff, Fathima S; Slifker, Michael; Hallmans, Goran; Toniolo, Paolo; Arslan, Alan A
2011 Sep;4(9):1457-1464, Cancer prevention research (Philadelphia, Pa.)
The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer. Cancer Prev Res; 4(9); 1457-64. (c)2011 AACR
— id: 137065, year: 2011, vol: 4, page: 1457, stat: Journal Article,

Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer
Chen, Tianhui; Surcel, Helja-Marja; Lundin, Eva; Kaasila, Marjo; Lakso, Hans-Ake; Schock, Helena; Kaaks, Rudolf; Koskela, Pentti; Grankvist, Kjell; Hallmans, Goran; Pukkala, Eero; Zeleniuch-Jacquotte, Anne; Toniolo, Paolo; Lehtinen, Matti; Lukanova, Annekatrin
2011 Feb;20(2):324-336, Cancer epidemiology biomarkers & prevention
BACKGROUND: Sex steroid hormones have been proposed to play a role in the development of non-epithelial ovarian cancers (NEOC) but so far no direct epidemiologic data are available. METHODS: A case-control study was nested within the Finnish Maternity Cohort, the world's largest biorepository of serum specimens from pregnant women. Study subjects were selected among women who donated a blood sample during a singleton pregnancy that led to the birth of their last child preceding diagnosis of NEOC. Case subjects were 41 women with sex cord stromal tumors (SCST) and 21 with germ cell tumors (GCT). Three controls, matching the index case for age, parity at the index pregnancy, and date at blood donation were selected (n = 171). OR and 95% CI associated with concentrations of testosterone, androstenedione, 17-OH-progesterone, progesterone, estradiol, and sex hormone-binding globulin (SHBG) were estimated through conditional logistic regression. RESULTS: For SCST, doubling of testosterone, androstenedione, and 17-OH-progesterone concentrations were associated with about 2-fold higher risk of SCST [ORs and 95% CI of 2.16 (1.25-3.74), 2.16 (1.20-3.87), and 2.62 (1.27-5.38), respectively]. These associations remained largely unchanged after excluding women within 2-, 4-, or 6-year lag time between blood donation and cancer diagnosis. Sex steroid hormones concentrations were not related to maternal risk of GCT. CONCLUSIONS: This is the first prospective study providing initial evidence that elevated androgens play a role in the pathogenesis of SCST. IMPACT: Our study may note a particular need for larger confirmatory investigations on sex steroids and NEOC
— id: 134152, year: 2011, vol: 20, page: 324, stat: Journal Article,

Endogenous hormones and coronary heart disease in postmenopausal women
Chen, Yu; Zeleniuch-Jacquotte, Anne; Arslan, Alan A; Wojcik, Oktawia; Toniolo, Paolo; Shore, Roy E; Levitz, Mortimer; Koenig, Karen L
2011 Jun;216(2):414-419, Atherosclerosis
The association between serum levels of endogenous estrogens in postmenopausal women and the subsequent risk of coronary heart disease (CHD) was examined in a prospective case-control study nested within the New York University Women's Health Study (NYUWHS). The NYUWHS is a prospective cohort study of 14,274 healthy women enrolled between 1985 and 1991. A total of 99 women who were postmenopausal and free of cardiovascular disease at enrollment and who subsequently experienced CHD, defined as non-fatal myocardial infarction (MI), fatal CHD, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG), were matched 1:2 by baseline age, blood sampling date, and postmenopausal status to controls who remained free of CHD as of the date of diagnosis of the matching case. Biochemical analyses for total estradiol, estrone, percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), and SHBG were performed on pre-diagnostic stored serum samples. Participants had not used any hormone medications in the 6 months prior to blood collection. In the model adjusting only for matching factors, the risk of CHD in the top tertile of calculated bioavailable estradiol was elevated compared with the bottom tertile (OR=2.10; 95% CI=1.13-3.90, P for trend=0.03), and the risk in the top tertile of SHBG was reduced (OR=0.50, 95% CI=0.28-0.92, P for trend<0.01). However, these associations disappeared after adjusting for baseline hypertension status, body mass index, and serum cholesterol levels. These findings suggest that circulating estradiol and SHBG are not associated with CHD risk in postmenopausal women beyond what can be explained by the variation in hypertension status, BMI, and cholesterol
— id: 134306, year: 2011, vol: 216, page: 414, stat: Journal Article,

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies
Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D
2011 Aug 23;105(5):709-722, British journal of cancer
BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk
— id: 137962, year: 2011, vol: 105, page: 709, stat: Journal Article,

Assessing the value of CAN-gene mutations using MALDI-TOF MS
Kohler, Corina; Tavelin, Bjorn; Fan, Alex Xiu-Cheng; Radpour, Ramin; Barekati, Zeinab; Levi, Fabio; Zhong, Xiao Yan; Lenner, Per; Toniolo, Paolo
2011 AUG ;137(8):1239-1244, Journal of cancer research & clinical oncology
Purpose To identify cancer-linked genes, Sjoblom et al. and Wood et al. performed a genome-wide mutation screening in human breast and colorectal cancers. 140 CAN-genes were found in breast cancer, which in turn contained overall 334 mutations. These mutations could prove useful for diagnostic and therapeutic purposes. Methods We used a MALDI-TOF MS 40-plex assay for testing 40 loci within 21 high-ranking breast cancer CAN-genes. To confirm mutations, we performed single-plex assays and sequencing. Results In general, the mutation rate of the analyzed loci in our sample cohort was very low. No mutation from the 40 loci analyzed could be found in the 6 cell lines. In tissue samples, a single breast cancer tissue sample showed heterozygosity at locus c.5834G > A within the ZFYVE26 gene (Zinc finger FYVE domain-containing gene 26). Conclusions Sjoblom et al./Wood et al. already showed that the vast majority of CAN-genes are mutated at very low frequency. Due to the fact that we only found one mutation in our cohort, we therefore assume that at the selected loci, mutations might be low-frequency events and therefore, more rarely detectable. However, further evaluation of the CAN-gene mutations in larger cohorts should be the aim of further studies
— id: 135633, year: 2011, vol: 137, page: 1239, stat: Journal Article,

Determinants of maternal sex steroids during the first half of pregnancy
Toriola A.T.; Vaarasmaki M.; Lehtinen M.; Zeleniuch-Jacquotte A.; Lundin E.; Rodgers K.-G.; Lakso H.-A.; Chen T.; Schock H.; Hallmans G.; Pukkala E.; Toniolo P.; Grankvist K.; Surcel H.-M.; Lukanova A.
2011 ;118(5):1029-1036, Obstetrics & gynecology
Objective: To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and estradiol (E2). Methods: We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression. Results: Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus. Conclusion: Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation. 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins
— id: 141088, year: 2011, vol: 118, page: 1029, stat: Journal Article,

Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case-control study
Toriola, Adetunji T.; Surcel, Helja-Marja; Lundin, Eva; Schock, Helena; Grankvist, Kjell; Pukkala, Eero; Chen, Tianhui; Toniolo, Paolo; Lehtinen, Matti; Zeleniuch-Jacquotte, Anne; Lukanova, Annekatrin
2011 NOV ;22(11):1607-1611, Cancer causes & control. ccc
Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC). A case-control study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case. Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58-1.62) or GCT (OR 1.13, 95% CI 0.51-2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85-1.43) or GCT (OR 0.93, 95% CI 0.68-1.28). Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC
— id: 140052, year: 2011, vol: 22, page: 1607, stat: Journal Article,

Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer
Toriola, Adetunji T; Lundin, Eva; Schock, Helena; Grankvist, Kjell; Pukkala, Eero; Chen, Tianhui; Zeleniuch-Jacquotte, Anne; Toniolo, Paolo; Lehtinen, Matti; Surcel, Helja-Marja; Lukanova, Annekatrin
2011 Aug;20(8):1798-1801, Cancer epidemiology biomarkers & prevention
BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-I have been associated with increased risk of developing breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. This study was conducted to further characterize the association of IGF-I during pregnancy with maternal breast cancer risk. METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women younger than 40 years, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched with each case on age and date at blood donation. Serum IGF-I concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate ORs and 95% CIs. RESULTS: No significant associations were observed between serum IGF-I concentrations and breast cancer risk in both the overall analysis (OR, 1.08; 95% CI, 0.80-1.47) and in analyses stratified by histologic subtype, lag time to cancer diagnosis, age at pregnancy, or age at diagnosis. CONCLUSION: There was no association between IGF-I and maternal breast cancer risk during early pregnancy in this large nested case-control study. IMPACT: Serum IGF-I concentrations during early pregnancy may not be related to maternal risk of developing breast cancer
— id: 137985, year: 2011, vol: 20, page: 1798, stat: Journal Article,

Postmenopausal circulating levels of 2- and 16alpha-hydroxyestrone and risk of endometrial cancer
Zeleniuch-Jacquotte, A; Shore, R E; Afanasyeva, Y; Lukanova, A; Sieri, S; Koenig, K L; Idahl, A; Krogh, V; Liu, M; Ohlson, N; Muti, P; Arslan, A A; Lenner, P; Berrino, F; Hallmans, G; Toniolo, P; Lundin, E
2011 Oct 25;105(9):1458-1464, British journal of cancer
Background:It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16alpha-hydroxy pathway is harmful.Methods:We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16alpha-hydroxyestrone (2-OHE1 : 16alpha-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16alpha-OHE1 were measured using a monoclonal antibody-based enzyme assay.Results:Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16alpha-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16alpha-OHE1 ratio.Conclusion:Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16alpha-OH pathway, protects against endometrial cancer
— id: 139737, year: 2011, vol: 105, page: 1458, stat: Journal Article,

IGF-I during primiparous pregnancy and maternal risk of breast cancer
Chen, Tianhui; Lukanova, Annekatrin; Grankvist, Kjell; Zeleniuch-Jacquotte, Anne; Wulff, Marianne; Johansson, Robert; Schock, Helena; Lenner, Per; Hallmans, Goran; Wadell, Goran; Toniolo, Paolo; Lundin, Eva
2010 May;121(1):169-175, Breast cancer research & treatment
Previously, we reported that insulin-like growth factor (IGF)-I during early pregnancy is positively associated with maternal risk of breast cancer. To further explore this association, we designed a new study limited to women who donated a blood sample during their first pregnancy ending with childbirth. A case-control study was nested within the Northern Sweden Maternity Cohort in which repository since 1975, serum specimens remaining after early pregnancy screening for infectious diseases had been preserved. Study subjects were selected among women who donated a blood sample during the full-term pregnancy that led to the birth of their first child. Two hundred and forty-four women with invasive breast cancer were eligible. Two controls, matching the index case for age and date at blood donation were selected (n = 453). IGF-I was measured in serum samples on an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. A significant positive association of breast cancer with IGF-I was observed, with OR of 1.73 (95% CI: 1.14-2.63) for the top tertile, P < 0.009. Subgroup analyses did not indicate statistical heterogeneity of the association by ages at sampling and diagnosis or by lag time to cancer diagnosis, although somewhat stronger associations with risk were observed in women < or = age 25 at index pregnancy and for cases diagnosed within 15 years of blood donation. The results of the study add further evidence for an adverse effect of elevated IGF-I concentrations during early reproductive life on risk of breast cancer
— id: 114698, year: 2010, vol: 121, page: 169, stat: Journal Article,

Maternal hormones during early pregnancy: a cross-sectional study
Chen, Tianhui; Lundin, Eva; Grankvist, Kjell; Zeleniuch-Jacquotte, Anne; Wulff, Marianne; Afanasyeva, Yelena; Schock, Helena; Johansson, Robert; Lenner, Per; Hallmans, Goran; Wadell, Goran; Toniolo, Paolo; Lukanova, Annekatrin
2010 May;21(5):719-727, Cancer causes & control. ccc
BACKGROUND: Little is known about correlates of first-trimester pregnancy hormones as in most studies maternal hormones have been measured later in gestation. We examined the associations of maternal characteristics and child sex with first-trimester maternal concentrations of four hormones implicated in breast cancer: human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), insulin-like growth factor (IGF)-I, and IGF-II. METHODS: About 338 serum samples donated to the Northern Sweden Maternity Cohort (NSMC), 1975-2001, during the first trimester of uncomplicated pregnancies, were analyzed for the hormones of interest as a part of a case-control study. The associations of maternal characteristics and child sex with hormone concentrations were investigated by correlation, general linear regression, and multivariate regression models. RESULTS: In the first trimester, greater maternal age was inversely correlated with IGF-I and IGF-II. In comparison with women carrying their first child, already parous women had higher IGF-I but lower hCG. Greater maternal weight and smoking were inversely correlated with hCG. No differences in hormone levels by child sex were observed. CONCLUSIONS: Our analyses indicated that potentially modifiable maternal characteristics (maternal weight and smoking) influence first-trimester pregnancy maternal hormone concentrations
— id: 114693, year: 2010, vol: 21, page: 719, stat: Journal Article,

Human chorionic gonadotropin in pregnancy and maternal risk of breast cancer
Toniolo, Paolo; Grankvist, Kjell; Wulff, Marianne; Chen, Tianhui; Johansson, Robert; Schock, Helena; Lenner, Per; Hallmans, Goran; Lehtinen, Matti; Kaaks, Rudolf; Wadell, Goran; Zeleniuch-Jacquotte, Anne; Lundin, Eva; Lukanova, Annekatrin
2010 Sep 1;70(17):6779-6786, Cancer research
Full-term pregnancies are associated with long-term reductions in maternal risk of breast cancer, but the biological determinants of the protection are unknown. Experimental observations suggest that human chorionic gonadotropin (hCG), a major hormone of pregnancy, could play a role in this association. A case-control study (242 cases and 450 controls) nested within the Northern Sweden Maternity Cohort included women who had donated a blood sample during the first trimester of a first full-term pregnancy. Total hCG was determined on Immulite 2000 analyzer. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. Maternal breast cancer risk decreased with increasing hCG (upper tertile OR, 0.67; CI, 0.46-0.99), especially for pregnancies before age 25 (upper tertile OR, 0.41; CI, 0.21-0.80). The association diverged according to age at diagnosis: risk was reduced after age 40 (upper tertile OR, 0.60; CI, 0.39-0.91) and seemed to increase before age 40 (upper tertile OR, 1.78; CI, 0.72-4.38). Risk was reduced among those diagnosed 10 years or longer after blood draw (upper tertile OR, 0.60; CI, 0.40-0.90), but not so among those diagnosed within 10 years (upper tertile OR, 4.33; CI, 0.86-21.7). These observations suggest that the association between pregnancy hCG and subsequent maternal risk of breast cancer is modified by age at diagnosis. Although the hormone seems to be a determinant of the reduced risk around or after age 50, it might not confer protection against, or it could even increase the risk of, cancers diagnosed in the years immediately following pregnancy
— id: 136565, year: 2010, vol: 70, page: 6779, stat: Journal Article,

Serum 25-hydroxyvitamin D and the risk of ovarian cancer
Toriola, Adetunji T; Surcel, Helja-Marja; Agborsangaya, Calypse; Grankvist, Kjell; Tuohimaa, Pentti; Toniolo, Paolo; Lukanova, Annekatrin; Pukkala, Eero; Lehtinen, Matti
2010 Jan;46(2):364-369, European journal of cancer
INTRODUCTION: Ecological and experimental studies suggest that vitamin D may be associated with a reduced risk of ovarian cancer. In this study, we sought to determine the risk of developing ovarian cancer according to serum 25-hydroxyvitamin D (25-OHD) concentrations assessed on average 5 years before the diagnosis. METHODS: We conducted a population-based longitudinal case-control study nested within the Finnish Maternity Cohort (FMC) which contains serum samples of virtually all pregnant women in Finland since 1983. Among them, 201 ovarian cancers diagnosed within 10 years of serum sampling were randomly selected as cases for this study. For each case, we selected two controls matched for age, parity and sampling season (+/-4 weeks) and one control matched for age and parity but for the opposite sampling season (6 months+/-4 weeks). RESULTS: The relative risks (estimated as odds ratio, OR) for ovarian cancer comparing the lowest quintile to the highest quintile of serum 25-OHD concentration were 1.8 (95% CI 0.9-3.5) among controls matched for the same season, and 1.1 (95% CI 0.6-2.2) among controls matched for the opposite season. The OR among women with insufficient (<75 nmol/L) serum 25-OHD concentration was 2.7 (95% CI 1.0-7.9, lower limit, 0.95) compared to that among those with sufficient (75 nmol/L) serum 25-OHD concentration. No differences in the point estimates were observed between serous or mucinous histological subtypes of ovarian cancer. CONCLUSION: Overall, we did not observe a significant association between serum 25-OHD concentrations and the risk of ovarian cancer. However, we found evidence suggestive of an increased risk among women with low to insufficient serum 25-OHD concentrations
— id: 114699, year: 2010, vol: 46, page: 364, stat: Journal Article,

Circulating vitamin d and risk of epithelial ovarian cancer
Arslan, Alan A; Clendenen, Tess V; Koenig, Karen L; Hultdin, Johan; Enquist, Kerstin; Agren, Asa; Lukanova, Annekatrin; Sjodin, Hubert; Zeleniuch-Jacquotte, Anne; Shore, Roy E; Hallmans, Goran; Toniolo, Paolo; Lundin, Eva
2009 ;2009:672492-672492, Journal of oncology
We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59-2.01). In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist
— id: 101966, year: 2009, vol: 2009, page: 672492, stat: Journal Article,

Circulating estrogen metabolites and risk for breast cancer in premenopausal women
Arslan, Alan A; Shore, Roy E; Afanasyeva, Yelena; Koenig, Karen L; Toniolo, Paolo; Zeleniuch-Jacquotte, Anne
2009 Aug;18(8):2273-2279, Cancer epidemiology biomarkers & prevention
BACKGROUND: It has been proposed that a shift toward 2-hydroxyestrone from 16alpha-hydroxyestrone metabolic pathway may be inversely associated with breast cancer risk because 2-hydroxyestrone is thought to be less genotoxic and estrogenic than 16alpha-hydroxyestrone. METHODS: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2-hydroxyestrone:16alpha-hydroxyestrone ratio in a case-control study on premenopausal women nested within a prospective cohort the New York University Women's Health Study. The serum levels of 2-hydroxyestrone and 16alpha-hydroxyestrone were measured in 377 incident premenopausal breast cancer cases and 377 premenopausal controls, who were matched on age at enrollment, number and dates of blood donations, and day and phase of menstrual cycle. RESULTS: Overall, no significant associations were observed between breast cancer risk and serum levels of 2-hydroxyestrone, 16alpha-hydroxyestrone, or their ratio. The 2-hydroxyestrone:16alpha-hydroxyestrone ratio was positively associated with risk for estrogen receptor-positive breast cancer in the analyses controlling for matching factors. However, the association was attenuated and not significant after adjustment for potential confounders (odds ratio for the highest versus the lowest quartile, 2.15; 95% CI, 0.88-5.27; P(trend) = 0.09). CONCLUSIONS: The results of the current study do not support the hypothesis that a metabolic shift from 16alpha-hydroxyestrone toward 2-hydroxyestrone in premenopausal women is associated with reduced risk for breast cancer. The association between the 2-hydroxy:16alpha-hydroxyestrone ratio and estrogen receptor-positive breast cancer needs to be explored in future studies
— id: 101449, year: 2009, vol: 18, page: 2273, stat: Journal Article,

Reproducibility of serum cytokines and growth factors
Gu, Yian; Zeleniuch-Jacquotte, Anne; Linkov, Faina; Koenig, Karen L; Liu, Mengling; Velikokhatnaya, Lyudmila; Shore, Roy E; Marrangoni, Adele; Toniolo, Paolo; Lokshin, Anna E; Arslan, Alan A
2009 Jan;45(1):44-49, Cytokine
BACKGROUND: In most studies, circulating biomarkers are usually assessed from a single sample, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested although it may not be valid for all biomarkers. The objective of this study was to investigate the temporal reproducibility of a panel of cytokines and growth factors. METHODS: Thirty-five postmenopausal women with two annual visits and 30 premenopausal women with three annual visits were randomly selected from the participants in an existing prospective cohort. A total of 23 serum cytokines, nine growth factors and C-reactive protein (CRP) were measured using the Luminex xMap technology. In addition, for eight biomarkers, regular and high sensitivity (hs) assays were compared. RESULTS: The biomarkers with adequate (>60%) detection rates and acceptable (> or =0.55) intra-class correlation coefficients (ICCs) were: hsIL-1beta, IL-1RA, hsIL-2, hsIL-4, hsIL-5, hsIL-6, hsIL-10, IL-12p40, hsIL-12p70, hsTNF-alpha, TNF-R1, TNF-R2, CRP, HGF, NGF, and EGFR. The remaining biomarkers either had low temporal reproducibility or were undetectable in more than 40% of samples. CONCLUSIONS: The results suggest that 16 of the 41 biomarkers measured with Luminex technology showed sufficient sensitivity and temporal reproducibility in sera
— id: 92177, year: 2009, vol: 45, page: 44, stat: Journal Article,

Reliability of tumor markers, chemokines, and metastasis-related molecules in serum
Linkov, Faina; Gu, Yian; Arslan, Alan A; Liu, Mengling; Shore, Roy E; Velikokhatnaya, Lyudmila; Koenig, Karen L; Toniolo, Paolo; Marrangoni, Adele; Yurkovetsky, Zoya; Zeleniuch-Jacquotte, Anne; Lokshin, Anna E
2009 Mar;20(1):21-26, European cytokine network
There is a growing interest in the role that cancer biomarkers, metastasis-related molecules, and chemokines may play in the development and progression of various cancers. However, few studies have addressed the reliability of such biomarkers in healthy individuals over time. The objective of this study was to investigate the temporal reliability of multiple proteins in serum samples from healthy women who donated blood over successive years. Thirty five, postmenopausal women with two, repeated annual visits, and thirty, premenopausal women with three, repeated annual visits were randomly selected among eligible subjects from an existing, prospective cohort. Multiplexing Luminex xMAPTM technology was used to measure the levels of 55 serum proteins representing cancer antigens, chemokines, angiogenic and anti-angiogenic factors, proteases, adipokines, apoptotic molecules, and other markers in these women. The biomarkers with high detection rates (> 60%) and acceptable reliability (intraclass correlation coefficient, ICCs > or = 0.55) using xMAPTM method were: cancer antigens: AFP, CA 15-3, CEA, CA-125, SCC, SAA; growth factors/related molecules: ErbB2, IGFBP-1; proteases and adhesion molecules: MMP-1, 8, 9, sE-selectin, human kallikreins (KLK) 8,10, ICAM-1, VCAM-1, chemokines: fractalkine, MCP-1,2, RANTES, MIP-1alpha, MIP-1beta, Eotaxin, GRO-alpha, IP-10; inhibitors of angiogenesis: angiostatin and endostatin; adipokines leptin and resistin; apoptotic factor: Fas, and other proteins mesothelin, myeloperoxidase (MPO), and PAI-1. The rest of the biomarkers under investigation either had ICCs less than 0.55 or had low levels of detection (< 60%). These included cancer antigens: CA 19-9, CA 72-4, MICA, S100, TTR, ULBP1, ULBP2, ULBP3; proteases: MMP 2, 3, 7, 12, 13; chemokines: MCP-3, MIF, MIG; adipokines: leptin and resistin; apoptotic factors: FasL, DR5, Cyfra 21-1; and inhibitors of angiogenesis and other markers: thrombospondin and heat shock protein (HSP) 27. In conclusion, 34 out of the 55 biomarkers investigated were present in detectable levels in > 60% of the samples, and with an ICC > or = 0.55, indicating that a single serum measurement can be used in prospective epidemiological studies using the xMAPTM method
— id: 126591, year: 2009, vol: 20, page: 21, stat: Journal Article,

C-reactive protein and ovarian cancer: a prospective study nested in three cohorts (Sweden, USA, Italy)
Lundin, Eva; Dossus, Laure; Clendenen, Tess; Krogh, Vittorio; Grankvist, Kjell; Wulff, Marianne; Sieri, Sabina; Arslan, Alan A; Lenner, Per; Berrino, Franco; Hallmans, Goran; Zeleniuch-Jacquotte, Anne; Toniolo, Paolo; Lukanova, Annekatrin
2009 Sep;20(7):1151-1159, Cancer causes & control. ccc
OBJECTIVES: Inflammatory processes may influence the risk of epithelial ovarian cancer, but available epidemiological evidence is limited and indirect. Circulating C-reactive protein (CRP), a sensitive marker of inflammation, may serve as a direct biological marker of an underlying association. METHODS: The association between ovarian cancer risk and pre-diagnostic circulating CRP was tested in a case-control study nested within three prospective cohorts from Sweden, USA, and Italy. The study included 237 cases and 427 individually matched controls. CRP was measured in stored blood samples by high-sensitivity immunoturbidimetric assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. RESULTS: Overall, CRP was not related to risk of ovarian cancer. However, a marked increase in risk was observed for CRP concentrations >10 mg/l: OR (95% CI) 4.4 (1.8-10.9), which remained significant after limiting analyses to cases diagnosed more than two or five years after blood donation (OR 3.0 (1.2-8.0) and 3.6 (1.0-13.2), respectively). Risk of mucinous tumors increased with high CRP, but the number of cases in this analysis was small. CONCLUSION: Study results offer additional support to the concept that chronic inflammation plays a role in epithelial ovarian cancer
— id: 114702, year: 2009, vol: 20, page: 1151, stat: Journal Article,

Reproducibility of serum pituitary hormones in women
Arslan, Alan A; Gu, Yian; Zeleniuch-Jacquotte, Anne; Koenig, Karen L; Liu, Mengling; Velikokhatnaya, Lyudmila; Shore, Roy E; Toniolo, Paolo; Linkov, Faina; Lokshin, Anna E
2008 Aug;17(8):1880-1883, Cancer epidemiology biomarkers & prevention
Endogenous pituitary hormones are commonly used in clinical and epidemiologic studies and some of them are thought to influence the risk of several diseases in women. In most studies, endogenous levels of pituitary hormones are usually assessed at a single point in time, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested and may not always be valid. This study examined the reproducibility of the following pituitary hormones: adrenocorticotropic hormone (ACTH), growth hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and prolactin, measured using the Luminex xMap method in sera of healthy premenopausal and postmenopausal women. The study included 30 premenopausal women with three yearly samples and 35 postmenopausal women with two repeated yearly samples randomly selected from an existing prospective cohort. Analysis of intraclass correlation coefficients suggested higher reproducibility in postmenopausal women compared with premenopausal women for the following hormones: FSH (0.72 and 0.37, respectively), LH (0.83 and 0.44, respectively), and growth hormone (0.60 and 0.35, respectively). The intraclass correlation coefficients were relatively high and similar between postmenopausal and premenopausal women for ACTH (0.95 and 0.94, respectively), TSH (0.85 and 0.85, respectively), and prolactin (0.72 and 0.69, respectively). This study found that serum concentrations of FSH, LH, and growth hormone are stable in postmenopausal women and that ACTH, TSH, and prolactin are stable in both premenopausal and postmenopausal women, suggesting that a single measurement may reliably categorize average levels over at least a 2-year period
— id: 91436, year: 2008, vol: 17, page: 1880, stat: Journal Article,

Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk
Brooks, Jennifer; Shore, Roy E; Zeleniuch-Jacquotte, Anne; Currie, Diane; Afanasyeva, Yelena; Koenig, Karen L; Arslan, Alan A; Toniolo, Paolo; Wirgin, Isaac
2008 Apr;17(4):1016-1019, Cancer epidemiology biomarkers & prevention
— id: 80287, year: 2008, vol: 17, page: 1016, stat: Journal Article,

Vitamin D receptor polymorphisms and risk of epithelial ovarian cancer
Clendenen, Tess V; Arslan, Alan A; Koenig, Karen L; Enquist, Kerstin; Wirgin, Isaac; Agren, Asa; Lukanova, Annekatrin; Sjodin, Hubert; Zeleniuch-Jacquotte, Anne; Shore, Roy E; Hallmans, Goran; Toniolo, Paolo; Lundin, Eva
2008 Feb 18;260(1-2):209-215, Cancer letters
The vitamin D receptor (VDR) is a critical mediator of the cellular effects of vitamin D. The associations between four common VDR polymorphisms (BSMI, APAI, TAQI, and FOKI) and risk of epithelial ovarian cancer (EOC) were assessed in a case-control study nested within two prospective cohorts. One hundred seventy incident cases of EOC and 323 individually matched controls were genotyped. Overall, no associations were observed in genotype analyses. Haplotypes combining three SNPs in high linkage disequilibrium (BSMI, APAI, and TAQI) were also not associated with risk. These observations do not support a role for BSMI, APAI, TAQI, and FOKI polymorphisms in epithelial ovarian cancer in a predominantly Caucasian population
— id: 76858, year: 2008, vol: 260, page: 209, stat: Journal Article,

Effect of long-term storage on hormone measurements in samples from pregnant women: the experience of the Finnish Maternity Cohort
Holl, Katsiaryna; Lundin, Eva; Kaasila, Marjo; Grankvist, Kjell; Afanasyeva, Yelena; Hallmans, Goran; Lehtinen, Matti; Pukkala, Eero; Surcel, Helja-Marja; Toniolo, Paolo; Zeleniuch-Jacquotte, Anne; Koskela, Pentti; Lukanova, Annekatrin
2008 ;47(3):406-412, Acta oncologica
Validity of biobank studies on hormone associated cancers depend on the extent the sample preservation is affecting the hormone measurements. We investigated the effect of long-term storage (up to 22 years) on immunoassay measurements of three groups of hormones and associated proteins: sex-steroids [estradiol, progesterone, testosterone, dihydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG)], pregnancy-specific hormones [human chorionic gonadotropin (hCG), placental growth hormone (pGH), alpha-fetoprotein (AFP)], and insulin-like growth factor (IGF) family hormones exploiting the world largest serum bank, the Finnish Maternity Cohort (FMC). Hormones of interest were analyzed in a random sample of 154 Finnish women in the median age (29.5 years, range 25 to 34 years) of their first pregnancy with serum samples drawn during the first trimester. All hormone measurements were performed using commercial enzyme-linked- or radio-immunoassays. Storage time did not correlate with serum levels of testosterone, DHEAS, hCG, pGH and total IGFBP-1. It had a weak or moderate negative correlation with serum levels of progesterone (Spearman's ranked correlation coefficient (r(s))=- 0.36), IGF-I (r(s)=-0.23) and IGF binding protein (BP)-3 (r(s)=-0.38), and weak positive correlation with estradiol (r(s)=0.23), SHBG (r(s)=0.16), AFP (r(s)=0.20) and non-phosphorylated IGF binding protein (BP)-1 (r(s)=0.27). The variation of all hormone levels studied followed the kinetics reported for early pregnancy. Bench-lag time (the time between sample collection and freezing for storage) did not materially affect the serum hormone levels. In conclusion, the stored FMC serum samples can be used to study hormone-disease associations, but close matching for storage time and gestational day are necessary design components of all related biobank studies
— id: 96693, year: 2008, vol: 47, page: 406, stat: Journal Article,

Human chorionic gonadotropin and alpha-fetoprotein concentrations in pregnancy and maternal risk of breast cancer: a nested case-control study
Lukanova, Annekatrin; Andersson, Ritu; Wulff, Marianne; Zeleniuch-Jacquotte, Anne; Grankvist, Kjell; Dossus, Laure; Afanasyeva, Yelena; Johansson, Robert; Arslan, Alan A; Lenner, Per; Wadell, Goran; Hallmans, Goran; Toniolo, Paolo; Lundin, Eva
2008 Dec 1;168(11):1284-1291, American journal of epidemiology
Pregnancy hormones are believed to be involved in the protection against breast cancer conferred by pregnancy. The authors explored the association of maternal breast cancer with human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP). In 2001, a case-control study was nested within the Northern Sweden Maternity Cohort, an ongoing study in which blood samples have been collected from first-trimester pregnant women since 1975. Cases (n = 210) and controls (n = 357) were matched for age, parity, and date of blood donation. Concentrations of hCG and AFP were measured by immunoassay. No overall significant association of breast cancer with either hCG or AFP was observed. However, women with hCG levels in the top tertile tended to be at lower risk of breast cancer than women with hCG levels in the lowest tertile in the whole study population and in subgroups of age at sampling, parity, and age at cancer diagnosis. A borderline-significant decrease in risk with high hCG levels was observed in women who developed breast cancer after the median lag time to cancer diagnosis (> or =14 years; odds ratio = 0.53, 95% confidence interval: 0.27, 1.03; P = 0.06). These findings, though very preliminary, are consistent with a possible long-term protective association of breast cancer risk with elevated levels of circulating hCG in the early stages of pregnancy
— id: 93616, year: 2008, vol: 168, page: 1284, stat: Journal Article,

Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk
Shore, Roy E; Zeleniuch-Jacquotte, Anne; Currie, Diane; Mohrenweiser, Harvey; Afanasyeva, Yelena; Koenig, Karen L; Arslan, Alan A; Toniolo, Paolo; Wirgin, Isaac
2008 May 1;122(9):2101-2105, International journal of cancer
To evaluate the associations of breast cancer risk with polymorphisms in the XPC and XPD/ERCC2 DNA nucleotide excision repair genes, a case-control study nested within a prospective cohort of 14,274 women was conducted. Genotypes were characterized for 612 incident, invasive breast cancer cases and their 1:1 matched controls. The homozygous variant of a poly(AT) insertion/deletion polymorphism in intron 9 of the XPC gene (XPC-PAT+/+), was associated with breast cancer risk [odds ratio (OR) = 1.45, 95% confidence interval: 1.07-1.97], after adjustment for other breast cancer risk factors. The breast cancer risk associated with XPC-PAT+/+ did not differ by age at diagnosis. There was an indication of an interaction (p = 0.08) between the XPC-PAT+/+ genotype and cigarette smoking. Ever smokers with the XPC-PAT+/+ genotype were at elevated risk of breast cancer (OR = 1.56, CI: 0.95-2.58), but no differences were observed among never smokers. Analyses of the ERCC2 Lys751Gln polymorphism did not show an association with breast cancer risk, either overall or at younger ages. The results suggest that breast cancer risk is related to the XPC haplotype tagged by the XPC-PAT+/+ insertion-deletion polymorphism in intron 9. Further study of the XPC haplotypes and their interactions with smoking in relation to breast cancer risk is needed
— id: 76390, year: 2008, vol: 122, page: 2101, stat: Journal Article,

Re: C-reactive protein and risk of breast cancer
Zeleniuch-Jacquotte, Anne; Gu, Yian; Bruning, Peter F; Bonfrer, Johannes M G; Koenig, Karen L; Arslan, Alan A; Toniolo, Paolo; Shore, Roy E
2008 Mar 19;100(6):443-444, Journal of the National Cancer Institute
— id: 93619, year: 2008, vol: 100, page: 443, stat: Journal Article,

Low birthweight in New York City and upstate New York following the events of September 11th
Eskenazi, Brenda; Marks, Amy R; Catalano, Ralph; Bruckner, Tim; Toniolo, Paolo G
2007 Nov;22(11):3013-3020, Human reproduction
BACKGROUND: We examined pregnancy outcomes in New York City (NYC) and upstate New York after the September 11, 2001 World Trade Center disaster. METHODS: Using birth certificate data for NY residents (n = 1,660,401 births), we estimated risk of low birthweight (LBW: <2,500 g) and preterm birth (<37 weeks) one week after September 11th versus three weeks before, and for 10 four-week intervals post-disaster versus these intervals in the two previous years. To corroborate regression results, we used time-series analysis. RESULTS: One week after September 11th in NYC, we observed an adjusted odds of 1.44 for births <1,500 g (P = 0.07) and 1.67 for births 1,500-1,999 g (P = 0.01), but a decreased odds of 2,000-2,499 g. We found no immediate change in LBW upstate or preterm in either location. In extended analyses, we found, in both locations, increased odds of <1,500-g births around New Year and 33-36 weeks post-disaster and decreased odds of moderate preterm for several weeks post-disaster. Time-series analyses yielded similar findings. CONCLUSIONS: The events of September 11, 2001 in NYC were associated with immediate increases in births <2,000 g, slightly delayed decreased preterm delivery, and delayed increases in LBW among infants exposed periconception or in the first two trimesters. Stress may contribute to observed associations
— id: 95021, year: 2007, vol: 22, page: 3013, stat: Journal Article,

Reliability of serum assays of iron status in postmenopausal women
Zeleniuch-Jacquotte, Anne; Zhang, Qi; Dai, Jisen; Shore, Roy E; Arslan, Alan A; Koenig, Karen L; Karkoszka, Jerzy; Afanasyeva, Yelena; Frenkel, Krystyna; Toniolo, Paolo; Huang, Xi
2007 May;17(5):354-358, Annals of epidemiology
PURPOSE: The aim of the study is to determine the reliability during a 2-year period of several newly developed iron-related assays to assess their potential for use in prospective epidemiologic studies. METHODS: We assessed the temporal reliability of several iron-related assays by using three serum samples collected at yearly intervals from 50 postmenopausal participants in a large prospective study. RESULTS: We observed high reliability coefficients for ferritin (0.78; 95% confidence interval [CI], 0.67-0.86), soluble transferrin receptor (sTfR; 0.79; 95% CI, 0.69-0.87), sTfR/ferritin ratio (0.74; 95% CI, 0.62-0.83), and hepcidin (0.89; 95% CI, 0.84-0.94). In a subset of 30 women, lower reliability was observed for serum iron (0.50; 95% CI, 0.29-0.70), unsaturated iron-binding capacity (0.55; 95% CI, 0.34-0.73), total iron-binding capacity (0.60; 95% CI, 0.40-0.76), and serum transferrin saturation rate (0.44; 95% CI, 0.22-0.65). The reliability of anti-5-hydroxymethyl-2'-deoxyuridine autoantibody titers, a biomarker of oxidized DNA damage, one of the mechanisms by which iron is thought to impact disease risk, was very high (0.97, 95% CI, 0.5-0.99). CONCLUSIONS: Our results show that some newly developed iron-related assays could be useful tools to assess iron-disease associations in prospective cohorts that collect a single blood sample
— id: 73252, year: 2007, vol: 17, page: 354, stat: Journal Article,

Effects of parity on pregnancy hormonal profiles across ethnic groups with a diverse incidence of breast cancer
Arslan, Alan A; Zeleniuch-Jacquotte, Anne; Lukanova, Annekatrin; Afanasyeva, Yelena; Katz, Joseph; Levitz, Mortimer; Del Priore, Giuseppe; Toniolo, Paolo
2006 Nov;15(11):2123-2130, Cancer epidemiology biomarkers & prevention
Epidemiologic evidence suggests that a full-term pregnancy may affect maternal risk of breast cancer later in life. The objective of this cross-sectional study was to compare circulating levels of maternal hormones affecting breast differentiation (human chorionic gonadotropin and prolactin) and proliferation [alpha-fetoprotein, insulin-like growth factor I (IGF-I), and estradiol] between women at a low to moderate risk (Asians and Hispanics), as compared with women at a high risk for breast cancer (Caucasians and African-Americans). Between May 2002 and December 2004, a total of 586 pregnant women were approached during a routine prenatal visit. Among them, 450 women (206 Caucasian, 126 Asian, 88 Hispanic, and 30 African-American) met the inclusion criteria and signed the informed consent. Only singleton pregnancies were considered. Blood samples were drawn during the second trimester of pregnancy. Laboratory analyses were done using the IMMULITE 2000 immunoassay system. Gestational age standardized mean levels of estradiol, IGF-I, and prolactin were significantly higher in Hispanic women compared with Caucasian women. Mean concentration of IGF-I was significantly higher in African-American women compared with Caucasian and Asian women. No significant differences in pregnancy hormone levels were observed between Caucasian and Asian (predominantly second-generation Chinese) women in this study. Irrespective of ethnicity, women who had their first pregnancy had substantially higher mean levels of alpha-fetoprotein, human chorionic gonadotropin, estradiol, and prolactin compared with women who previously had at least one full-term pregnancy. These data suggest that circulating pregnancy hormone levels may explain some of the ethnic differences in breast cancer risk
— id: 72078, year: 2006, vol: 15, page: 2123, stat: Journal Article,

Early serum hCG after in vitro fertilization (IVF) differs depending on day of embryo transfer
Keegan, DA; Salas, J; Liu, M; Lukanova, A; Toniolo, P; Grifo, JA
2006 SEP ;86(1-2):S226-S226, Fertility & sterility
— id: 70636, year: 2006, vol: 86, page: S226, stat: Journal Article,

Insulin-like growth factor I in pregnancy and maternal risk of breast cancer
Lukanova, Annekatrin; Toniolo, Paolo; Zeleniuch-Jacquotte, Anne; Grankvist, Kjell; Wulff, Marianne; Arslan, Alan A; Afanasyeva, Yelena; Johansson, Robert; Lenner, Per; Hallmans, Goran; Wadell, Goran; Lundin, Eva
2006 Dec;15(12):2489-2493, Cancer epidemiology biomarkers & prevention
BACKGROUND: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy. METHODS: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II. CONCLUSIONS: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy
— id: 71414, year: 2006, vol: 15, page: 2489, stat: Journal Article,

Early serum hCG after in vitro fertilization: Can we predict multiple gestations?
Salas, J; Keegan, DA; Liu, M; Toniolo, P; Grifo, JA
2006 SEP ;86(1-2):S134-S135, Fertility & sterility
— id: 70628, year: 2006, vol: 86, page: S134, stat: Journal Article,

Predictive value of early serum beta-hCG on pregnancy outcome after in vitro fertilization
Salas, J; Keegan, DA; Liu, ML; Lukanova, A; Toniolo, P; Grifo, JA
2006 FEB ;13(2):158A-158A, Journal of the Society for Gynecologic Investigation
— id: 62828, year: 2006, vol: 13, page: 158A, stat: Journal Article,

Circulating enterolactone and risk of endometrial cancer
Zeleniuch-Jacquotte, Anne; Lundin, Eva; Micheli, Andrea; Koenig, Karen L; Lenner, Per; Muti, Paola; Shore, Roy E; Johansson, Ingegerd; Krogh, Vittorio; Lukanova, Annekatrin; Stattin, Par; Afanasyeva, Yelena; Rinaldi, Sabina; Arslan, Alan A; Kaaks, Rudolf; Berrino, Franco; Hallmans, Goran; Toniolo, Paolo; Adlercreutz, Herman
2006 Nov 15;119(10):2376-2381, International journal of cancer
It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer
— id: 69245, year: 2006, vol: 119, page: 2376, stat: Journal Article,

Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review
Arslan, Alan A; Gold, Leslie I; Mittal, Khushbakhat; Suen, Ting-Chung; Belitskaya-Levy, Ilana; Tang, Moon-Shong; Toniolo, Paolo
2005 Apr;20(4):852-863, Human reproduction
BACKGROUND: Uterine leiomyomas are extremely common and a major cause of pelvic pain, bleeding, infertility, and the leading indication for hysterectomy. Familial and epidemiological studies provide compelling evidence that genetic alterations play an important role in leiomyoma development. METHODS: Using Affymetrix U133A GeneChip we analysed expression profiles of 22,283 genes in paired samples of leiomyoma and adjacent normal myometrium. We compared our results with previously published data on gene expression in uterine leiomyoma and identified the overlapping gene alterations. RESULTS: We detected 80 genes with average differences of > or = 2-fold and false discovery rates of < 5% (14 overexpressed and 66 underexpressed). A comparative analysis including eight previous gene expression studies revealed eight prominent genes (ADH1, ATF3, CRABP2, CYR61, DPT, GRIA2, IGF2, MEST) identified by at least five different studies, eleven genes (ALDH1, CD24, CTGF, DCX, DUSP1, FOS, GAGEC1, IGFBP6, PTGDS, PTGER3, TYMS) reported by four studies, twelve genes (ABCA, ANXA1, APM2, CCL21, CDKN1A, CRMP1, EMP1, ESR1, FY, MAP3K5, TGFBR2, TIMP3) identified by three studies, and 40 genes reported by two different studies. CONCLUSIONS: Review of gene expression data revealed concordant changes in genes regulating retinoid synthesis, IGF metabolism, TGF-beta signaling and extracellular matrix formation. Gene expression studies provide clues to the relevant pathways of leiomyoma development
— id: 55957, year: 2005, vol: 20, page: 852, stat: Journal Article,

Ethical, legal, and social issues related to genomics and cancer research: the impending crisis
Ellerin, Bruce E; Schneider, Robert J; Stern, Arnold; Toniolo, Paolo G; Formenti, Silvia C
2005 Nov;2(11):919-926, Journal of the American College of Radiology : JACR
Cancer research is a multibillion-dollar enterprise validated by the clinical trial process and increasingly defined by genomics. The continued success of the endeavor depends on the smooth functioning of the clinical trial system, which in turn depends on human subject participation. Yet human subject participation can exist only in an atmosphere of trust between research participants and research sponsors, and the advent of genomics has raised a multitude of ethical, legal, and social issues that threaten this trust. The authors examine 6 of these issues: (1) informed consent; (2) privacy, confidentiality, and family disclosure dilemmas; (3) property rights in genomic discoveries; (4) individual and institutional conflicts of interest; (5) insurance and employment issues; and (6) litigation under the federal False Claims Act. The authors conclude that failure to resolve these issues may lead to a sufficient impairment of trust in genomics-based clinical trials on the part of potential research participants that the clinical trial system may implode for lack of willing participants, thus threatening the future of cancer research
— id: 72043, year: 2005, vol: 2, page: 919, stat: Journal Article,

Insulin-like growth factor-I, IGF binding protein-3, and breast cancer in young women: a comparison of risk estimates using different peptide assays
Rinaldi, Sabina; Kaaks, Rudolf; Zeleniuch-Jacquotte, Anne; Arslan, Alan A; Shore, Roy E; Koenig, Karen L; Dossus, Laure; Riboli, Elio; Stattin, Par; Lukanova, Annekatrin; Toniolo, Paolo
2005 Jan;14(1):48-52, Cancer epidemiology biomarkers & prevention
Circulating insulin-like growth factor-I (IGF-I) and its major binding protein IGF binding protein-3 (IGFBP-3) have been associated with increased risk of premenopausal breast cancer, although risk estimates varied broadly. An extension of a case-control study (138 cases, 259 matched controls) on IGF-I and breast cancer in premenopausal women nested in the New York University Women's Health Study cohort offered the opportunity to address the hypothesis that such variability may have been the result of variations in the ability of different IGFBP-3 assays to specifically measure intact/functional forms of the protein. IGF-I and IGFBP-3 had originally been measured using in-house RIAs. These measurements were repeated using commercially available ELISAs [Diagnostic System Laboratories (DSL), Webster, Texas], and a third ELISA with greater specificity for active forms for IGFBP-3. Pearson's correlations between IGF-I concentrations in the original study and DSL ELISA were very high [r = 0.92; 95% CI, 0.90-0.94]. Correlations with DSL ELISA were much lower for IGFBP-3 (r = 0.58; 0.49-0.66) and even lower still with the assay for functional IGFBP-3 (r = 0.33; 0.20-0.44). IGF-I and IGFBP-3 measurements by the DSL ELISA methods showed statistically significant relationships with risk. The odds ratios (OR) for top versus bottom quartiles were 1.93 (1.00-3.72; P = 0.02) and 2.03 (1.09-3.76; P = 0.02), respectively, in agreement with the original observations. In contrast, measurements of functional IGFBP-3 tended to be unrelated to risk [ORs for the top versus bottom quartile, 0.97 (0.44-2.11)]. The association with IGF-I became substantially weaker and lost statistical significance after adjustment for IGFBP-3 using DSL ELISA, but became considerably stronger when adjusting for the functional IGFBP-3 measurements [OR = 2.43 (1.21-4.90); P = 0.005], or when considering the molar ratio of IGF-I to IGFBP-3 [OR = 2.37 (1.13-5.00); P = 0.02]. These results are consistent with an association of breast cancer risk in young women with elevated IGF-I and IGFBP-3, and show that for IGFBP-3, the strength of such an association could vary substantially depending on the assay used
— id: 72082, year: 2005, vol: 14, page: 48, stat: Journal Article,

IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three prospective studies
Rinaldi, Sabina; Toniolo, Paolo; Muti, Paola; Lundin, Eva; Zeleniuch-Jacquotte, Anne; Arslan, Alan; Micheli, Andrea; Lenner, Per; Dossus, Laure; Krogh, Vittorio; Shore, Roy E; Koenig, Karen L; Riboli, Elio; Stattin, Par; Berrino, Franco; Hallmans, Goran; Lukanova, Annekatrin; Kaaks, Rudolf
2005 Dec;14(6):493-496, European journal of cancer prevention
Prospective cohort studies on breast cancer risk among premenopausal women and insulin-like growth factor I (IGF-I) concentrations have so far included only few cases, and have shown inconsistent relative risk estimates. We pooled 220 cases of breast cancer diagnosed before age 50, and 434 control subjects, from three prospective studies in New York (USA), Umea (Northern Sweden) and Milan (Italy), and we measured IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) with common enzyme-linked immunosorbent assays. Overall, IGF-I and IGFBP-3 measurements obtained by the common method showed a positive but not significant relationship with breast cancer risk (odds ratios (ORs) 0.90 [95% confidence intervals (95% CI) 0.50-1.62], 1.63 [0.89-2.97], 1.46 [0.78-2.73] and 1.41 [0.75-2.63] for quintiles of IGF-I, and ORs 0.98 [0.54-1.75], 1.06 [0.59-1.91], 1.04 [0.58-1.87] and 1.77 [0.97-3.24] for quintiles of IGFBP-3). Our results give only moderate support for an association of blood IGF-I with breast cancer risk in young women
— id: 72088, year: 2005, vol: 14, page: 493, stat: Journal Article,

The challenge of measuring circulating estradiol at low concentrations
Toniolo, Paolo; Lukanova, Annekatrin
2005 ;7(2):45-47, Breast cancer research
Demand for measuring estradiol at low concentrations is increasing, and the widely used 'direct' radioimmunoassays that do not require a preliminary organic purification step may be inadequate in patient care because of their limited accuracy. In observational epidemiology, however, the main concern is to obtain a correct ranking of individuals' hormone concentration relative to the true level (as determined through a 'gold standard'). Despite differences in the absolute scale of measured and true concentrations, correct ranking will permit calculation of unbiased estimates of hormone-disease associations. In prospective studies, the major concerns are the limited volume of often irreplaceable specimens and the need to perform a large number of assays within a reasonable period of time. Organic purification is often not feasible because of sample volume requirements and logistic difficulties, and so the development of accurate, rapid and inexpensive methods to measure sex steroids at low concentrations would represent a valuable new research tool for both clinicians and epidemiologists
— id: 62358, year: 2005, vol: 7, page: 45, stat: Journal Article,

Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: results of a prospective study
Zeleniuch-Jacquotte, Anne; Gu, Yian; Shore, Roy E; Koenig, Karen L; Arslan, Alan A; Kato, Ikuko; Rinaldi, Sabina; Kaaks, Rudolf; Toniolo, Paolo
2005 Mar 20;114(2):323-327, International journal of cancer
We report on a prospective study to assess the association of postmenopausal serum levels of sex hormones with subsequent risk of breast carcinoma in situ. We conducted a case-control study nested within the cohort of the New York University Women's Health Study, a large prospective study documenting a positive association of circulating levels of estrogens and androgens with invasive breast cancer. The study included 69 cases of incident in situ carcinoma and 134 individually matched controls. No statistically significant trend of increasing risk with increasing level of any of the hormones was observed. Odds ratios (95% CIs) for the highest tertile relative to the lowest were 1.10 (0.51-2.39) for estradiol, 0.95 (0.41-2.19) for estrone, 1.63 (0.69-3.88) for testosterone, 0.99 (0.44-2.24) for androstenedione, 0.99 (0.45-2.20) for dehydroepiandrosterone sulfate and 0.81 (0.38-1.74) for sex hormone-binding globulin. Adjusting for potential confounders did not materially affect the results, nor did limiting the analysis to the 59 cases of ductal carcinoma in situ, the lesion thought to be the direct precursor of most invasive breast cancers. Our results are at variance with the positive associations observed in this same cohort with risk of invasive breast cancer. Possible explanations for our results include lack of power, an effect of sex hormones limited to the progression from in situ to invasive tumors, overrepresentation of indolent tumors or an effect of sex hormones on the induction of only a subset of in situ tumors, those that would develop into invasive tumors
— id: 51094, year: 2005, vol: 114, page: 323, stat: Journal Article,

Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies
Cho, Eunyoung; Smith-Warner, Stephanie A; Spiegelman, Donna; Beeson, W Lawrence; van den Brandt, Piet A; Colditz, Graham A; Folsom, Aaron R; Fraser, Gary E; Freudenheim, Jo L; Giovannucci, Edward; Goldbohm, R Alexandra; Graham, Saxon; Miller, Anthony B; Pietinen, Pirjo; Potter, John D; Rohan, Thomas E; Terry, Paul; Toniolo, Paolo; Virtanen, Mikko J; Willett, Walter C; Wolk, Alicja; Wu, Kana; Yaun, Shiaw-Shyuan; Zeleniuch-Jacquotte, Anne; Hunter, David J
2004 Jul 7;96(13):1015-1022, Journal of the National Cancer Institute
BACKGROUND: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. METHODS: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and > or =250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively (P(trend)<.001). Calcium intake was also inversely related to the risk of colorectal cancer. The relative risk for the highest versus the lowest quintile of intake was 0.86 (95% CI = 0.78 to 0.95; P(trend) =.02) for dietary calcium and 0.78 (95% CI = 0.69 to 0.88; P(trend)<.001) for total calcium (combining dietary and supplemental sources). These results were consistent across studies and sex. The inverse association for milk was limited to cancers of the distal colon (P(trend)<.001) and rectum (P(trend) =.02). CONCLUSION: Higher consumption of milk and calcium is associated with a lower risk of colorectal cancer
— id: 44778, year: 2004, vol: 96, page: 1015, stat: Journal Article,

Comparison between hospitalized and screening controls in studies assessing breast cancer risk
Garbers, Samantha; Dubin, Neil; Toniolo, Paolo; Wynder, E L; Taioli, Emanuela
2004 Jun;91(6):E211-E224, Bulletin du cancer
BACKGROUND: In case-control studies, selection of an appropriate group of controls is a critical step which may affect the outcome of the analysis. METHODS: We studied the differences in reproductive, lifestyle, and anthropometric variables between controls from a hospital-based study and controls from a screening clinic. Odds ratios for breast cancer were calculated using the two types of controls, and the impact on the resulting odds ratio was studied. RESULTS: Some interesting differences in odds ratios obtained with the two sets of controls were found. Among premenopausal screening subjects, the odds ratio for breast cancer did not change across quartiles of body mass,while among hospital subjects, the risk of breast cancer significantly decreased with increasing body mass. For liquor and beer consumption, a three-fold increase in breast cancer risk was observed among premenopausal hospital subjects, whereas no association was found among screening subjects. Among postmenopausal women, a significant decrease in breast cancer risk with ovariectomy was only observed in the hospital-based study. CONCLUSIONS: Our results suggest that in examining the association between body mass, alcohol consumption, or ovariectomy and breast cancer risk, the choice of control group used should be carefully considered
— id: 47822, year: 2004, vol: 91, page: E211, stat: Journal Article,

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women
Lukanova, A; Lundin, E; Zeleniuch-Jacquotte, A; Muti, P; Mure, A; Rinaldi, S; Dossus, L; Micheli, A; Arslan, A; Lenner, P; Shore, R E; Krogh, V; Koenig, K L; Riboli, E; Berrino, F; Hallmans, G; Stattin, P; Toniolo, P; Kaaks, R
2004 Feb;150(2):161-171, European journal of endocrinology
OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women
— id: 44748, year: 2004, vol: 150, page: 161, stat: Journal Article,

Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women
Lukanova, Annekatrin; Lundin, Eva; Micheli, Andrea; Arslan, Alan; Ferrari, Pietro; Rinaldi, Sabina; Krogh, Vittorio; Lenner, Per; Shore, Roy E; Biessy, Carine; Muti, Paola; Riboli, Elio; Koenig, Karen L; Levitz, Mortimer; Stattin, Par; Berrino, Franco; Hallmans, Goran; Kaaks, Rudolf; Toniolo, Paolo; Zeleniuch-Jacquotte, Anne
2004 Jan 20;108(3):425-432, International journal of cancer
Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis
— id: 44750, year: 2004, vol: 108, page: 425, stat: Journal Article,

Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer
Lukanova, Annekatrin; Zeleniuch-Jacquotte, Anne; Lundin, Eva; Micheli, Andrea; Arslan, Alan A; Rinaldi, Sabina; Muti, Paola; Lenner, Per; Koenig, Karen L; Biessy, Carine; Krogh, Vittorio; Riboli, Elio; Shore, Roy E; Stattin, Par; Berrino, Franco; Hallmans, Goran; Toniolo, Paolo; Kaaks, Rudolf
2004 Jan 10;108(2):262-268, International journal of cancer
Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer
— id: 44751, year: 2004, vol: 108, page: 262, stat: Journal Article,

The changing demographics of head and neck squamous cell carcinoma in the United States
Sikora, Andrew G; Toniolo, Paolo; DeLacure, Mark D
2004 Nov;114(11):1915-1923, Laryngoscope
OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCCA) has declined in the United States since the late 1970s. During this time, substantial immigration from other countries has occurred, and the average lifespan has increased. We tested the hypothesis that these trends have altered the HNSCCA patient population. STUDY DESIGN: Retrospective analysis was made of population-based data from the SEER database, a national registry capturing roughly 10% of all U.S. cancer diagnoses. METHODS: We examined all unique diagnoses of HNSCCA in the database from 1976 to 1999 and determined the breakdown of cases by age, sex, and race. RESULTS: The absolute number of new HNSCCA diagnoses per year declined overall by 5% during the time period of the study, whereas new diagnoses in patients older than 74 years of age increased by more than 20%. The rate of HNSCCA per 100,000 person-years in elderly women did not change, and the rate in elderly men decreased, indicating that the observed increase in cases is explained by a growing population of elderly persons at risk. An increase in the absolute number of cases, but not the incidence rate, was also seen among persons younger than 50 years of age. Although both the absolute number of new cases and the incidence rates of HNSCCA in white male patients declined substantially, the percentage of HNSCCA patients classified as minorities increased from 14.5% to more than 20% of all cases. During the time period of the study, the overall number of HNSCCA cases in nonwhite and Hispanic patients increased by 36%. CONCLUSION: Increasing numbers of elderly and minority patients with HNSCCA are likely to alter patterns of disease and utilization of health care resources
— id: 48079, year: 2004, vol: 114, page: 1915, stat: Journal Article,

Circulating enterolactone and risk of breast cancer: a prospective study in New York
Zeleniuch-Jacquotte, A; Adlercreutz, H; Shore, R E; Koenig, K L; Kato, I; Arslan, A A; Toniolo, P
2004 Jul 5;91(1):99-105, British journal of cancer
It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.British Journal of Cancer (2004) 91, 99-105. doi:10.1038/sj.bjc.6601893 www.bjcancer.com
— id: 43220, year: 2004, vol: 91, page: 99, stat: Journal Article,

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study
Zeleniuch-Jacquotte, A; Shore, R E; Koenig, K L; Akhmedkhanov, A; Afanasyeva, Y; Kato, I; Kim, M Y; Rinaldi, S; Kaaks, R; Toniolo, P
2004 Jan 12;90(1):153-159, British journal of cancer
We assessed the association of sex hormone levels with breast cancer risk in a case-control study nested within the cohort of 7054 New York University (NYU) Women's Health Study participants who were postmenopausal at entry. The study includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and 563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for breast cancer for the highest quintile of each hormone and sex-hormone binding globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47-4.21), P(trend)=0.003 for oestradiol; 3.24 (1.87-5.58), P(trend)<0.001 for oestrone; 2.37 (1.39-4.04), P(trend)=0.002 for testosterone; 2.07 (1.28-3.33), P(trend)<0.001 for androstenedione; 1.74 (1.05-2.89), P(trend)<0.001 for dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31-0.82), P(trend)<0.001 for SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years prior to diagnosis showed results in the same direction as overall analyses, although the tests for trend did not reach statistical significance for DHEAS and SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95 cases and their matched controls who had given a second blood donation within 5 years of diagnosis, were of small magnitude and overall not different in cases and controls. The association of androgens with risk did not persist after adjustment for oestrone (1.08, 95% CI=0.92-1.26 for testosterone; 1.15, 95% CI=0.95-1.39 for androstenedione and 1.06, 95% CI=0.90-1.26 for DHEAS), the oestrogen most strongly associated with risk in our study. Our results support the hypothesis that the associations of circulating oestrogens with breast cancer risk are more likely due to an effect of circulating hormones on the development of cancer than to elevations induced by the tumour. They also suggest that the contribution of androgens to risk is largely through their role as substrates for oestrogen production
— id: 42623, year: 2004, vol: 90, page: 153, stat: Journal Article,

Circulating soluble Fas levels and risk of ovarian cancer
Akhmedkhanov, Arslan; Lundin, Eva; Guller, Seth; Lukanova, Annekatrin; Micheli, Andrea; Ma, Yuehong; Afanasyeva, Yelena; Zeleniuch-Jacquotte, Anne; Krogh, Vittorio; Lenner, Per; Muti, Paola; Rinaldi, Sabina; Kaaks, Rudolf; Berrino, Franco; Hallmans, Goran; Toniolo, Paolo
2003 Dec 22;3(1):33-33, BMC cancer
BACKGROUND: Dysregulation of apoptosis, specifically overexpression of soluble Fas (sFas), has been proposed to play a role in the development of ovarian cancer. The main objective of the present study was to evaluate serum sFas as a potential biomarker of ovarian cancer risk. METHODS: The association between serum sFas levels and the risk of ovarian cancer was examined in a case-control study nested within three prospective cohorts in New York (USA), Umea (Sweden), and Milan (Italy). Case subjects were 138 women with primary invasive epithelial ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood donation. Control subjects were 263 women who were free of cancer, and matched the case on cohort, menopausal status, age, and enrollment date. Serum sFas levels were determined using a quantitative sandwich enzyme immunoassay. RESULTS: Serum sFas levels were similar in women subsequently diagnosed with ovarian cancer (median, 6.5 ng/mL; range, 4.4-10.2) and in controls (median, 6.8 ng/mL; range, 4.5-10.1). Statistically significant trends of increasing serum sFas with age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p < 0.0001). Compared to women in the lowest third, women in the highest third of serum sFas were not at increased risk of ovarian cancer after adjustment for potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42-1.82). CONCLUSION: The results suggest that serum sFas may not be a suitable marker for identification of women at increased risk of ovarian cancer
— id: 44780, year: 2003, vol: 3, page: 33, stat: Journal Article,

Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women
Ali, M Aktar; Akhmedkhanov, Arslan; Zeleniuch-Jaquotte, Anne; Toniolo, Paolo; Frenkel, Krystyna; Huang, Xi
2003 ;27(2):116-121, Cancer detection & prevention
Reliability of serum levels of iron, ferritin and nitrite (NO(2)(-)) over a 2-year period were evaluated in 40 healthy women (20 pre-menopausal and 20 post-menopausal), ages 39-65 years, from the New York University Women's Health Study (NYUWHS). Three blood samples per woman collected at yearly intervals were analyzed. Reliability coefficients (RCs) of serum iron, ferritin, and nitrite were 0.03 (95% confidence interval (CI), 0-0.33), 0.90 (95% CI, 0.79-0.95), and 0.72 (95% CI, 0.50-0.86), respectively, for pre-menopausal women, and 0.26 (95% CI, 0-0.56), 0.77 (95% CI, 0.59-0.89), and 0.55 (95% CI, 0.30-0.77), respectively, for post-menopausal women. In a case-control study nested within NYUWHS cohort, serum levels of nitrite, ferritin, and iron were measured in women apparently healthy at the time of blood donation but diagnosed with renal cancer 1.8-12.2 years later (n=24) and in individually matched controls (two per case). The results suggest that high serum levels of ferritin and nitrite may be associated with a decreased risk of renal cancer (odds ratio (OR), 0.55, 95% CI, 0.15-2.01 for ferritin, and OR, 0.52, 95% CI, 0.17-1.60 for nitrite in women with above median level as compared to women with below median level). The possible role of ferritin and nitrite in renal cancer is discussed
— id: 34537, year: 2003, vol: 27, page: 116, stat: Journal Article,

Reliability of follicle-stimulating hormone measurements in serum
Arslan, Alan A; Zeleniuch-Jacquotte, Anne; Lukanova, Annekatrin; Rinaldi, Sabina; Kaaks, Rudolf; Toniolo, Paolo
2003 Jun 18;1(1):49-49, Reproductive biology & endocrinology: RB&E.
BACKGROUND: Follicle-stimulating hormone (FSH), a member of gonadotropin family, is critical for follicular maturation and ovarian steroidogenesis. Serum FSH levels are known to fluctuate during different phases of menstrual cycle in premenopausal women, and increase considerably after the menopause as a result of ovarian function cessation. There is little existing evidence to guide researchers in estimating the reliability of serum FSH measurements. The objective of this study was to assess the reliability of FSH measurement using stored sera from an ongoing prospective cohort - the NYU Women's Health Study. METHODS: Sixty healthy women (16 premenopausal, 44 postmenopausal), who donated at least two blood samples at approximately 1-year intervals were studied. An immunoradiometric assay using a sandwich monoclonal antibodies technique was used to measure FSH levels in serum. RESULTS: The reliability of a single log-transformed FSH measurement, as determined by the intraclass correlation coefficient, was 0.70 for postmenopausal women (95% confidence interval (CI), 0.55-0.82) and 0.09 for premenopausal women (95% CI, 0-0.54). CONCLUSIONS: These results suggest that a single measurement is sufficient to characterize the serum FSH level in postmenopausal women and could be a useful tool in epidemiological research. For premenopausal women, however, the reliability coefficient was low, suggesting that a single determination is insufficient to reliably estimate a woman's true average serum FSH level and repeated measurements are desirable
— id: 38098, year: 2003, vol: 1, page: 49, stat: Journal Article,

Serum follicle-stimulating hormone and risk of epithelial ovarian cancer in postmenopausal women
Arslan, Alan A; Zeleniuch-Jacquotte, Anne; Lundin, Eva; Micheli, Andrea; Lukanova, Annekatrin; Afanasyeva, Yelena; Lenner, Per; Krogh, Vittorio; Muti, Paola; Rinaldi, Sabina; Kaaks, Rudolf; Berrino, Franco; Hallmans, Goran; Toniolo, Paolo
2003 Dec;12(12):1531-1535, Cancer epidemiology biomarkers & prevention
The 'gonadotropin hypothesis' postulates that gonadotropin overstimulation of ovarian epithelium results in its increased proliferation and subsequent malignant transformation. To address this hypothesis, we assessed the association between prediagnostic serum levels of follicle-stimulating hormone (FSH) and the risk of epithelial ovarian cancer in postmenopausal women who were part of a case-control study nested within three prospective cohorts in New York City, Umea, Sweden, and Milan, Italy. Case subjects were 88 women with primary invasive epithelial ovarian cancer diagnosed between 3 months and 13.1 years after the blood donation. Controls were 168 women who were free of cancer and matched the case on cohort, age, and enrollment date. Serum FSH was determined using a quantitative immunoradiometric assay. FSH concentrations were similar in women who subsequently received a diagnosis of epithelial ovarian cancer (median, 44.0 mIU/ml; range, 13.8-101.2) and in controls (median, 43.4 mIU/ml; range, 13.5-109.5; P = 0.17). Compared with women in the lowest third, women in the highest third of serum FSH were not at increased risk of epithelial ovarian cancer after an adjustment for potential confounders (odds ratio, 0.85; 95% confidence interval, 0.36-1.99). These observations provide no evidence for an association between circulating FSH and risk of epithelial ovarian cancer in postmenopausal women and do not appear to support the gonadotropin hypothesis of epithelial ovarian carcinogenesis
— id: 44779, year: 2003, vol: 12, page: 1531, stat: Journal Article,

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women
Key, T J; Appleby, P N; Reeves, G K; Roddam, A; Dorgan, J F; Longcope, C; Stanczyk, F Z; Stephenson, H E Jr; Falk, R T; Miller, R; Schatzkin, A; Allen, D S; Fentiman, I S; Key, T J; Wang, D Y; Dowsett, M; Thomas, H V; Hankinson, S E; Toniolo, P; Akhmedkhanov, A; Koenig, K; Shore, R E; Zeleniuch-Jacquotte, A; Berrino, F; Muti, P; Micheli, A; Krogh, V; Sieri, S; Pala, V; Venturelli, E; Secreto, G; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Kuller, L H; Cummings, S R; Helzlsouer, K J; Alberg, A J; Bush, T L; Comstock, G W; Gordon, G B; Miller, S R; Longcope, C
2003 Aug 20;95(16):1218-1226, Journal of the National Cancer Institute
BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol
— id: 38442, year: 2003, vol: 95, page: 1218, stat: Journal Article,

Free estradiol and breast cancer risk in postmenopausal women: Comparison of measured and calculated values
Key, TJ; Appleby, PN; Reeves, GK; Roddam, AW; Dorgan, JF; Longcope, C; Stanczyk, FZ; Stephenson, HE; Falk, RT; Miller, R; Schatzkin, A; Allen, DS; Fentiman, IS; Key, TJ; Wang, DY; Thomas, HV; Hankinson, SE; Toniolo, P; Akhmedkhanov, A; Koenig, K; Shore, RE; Zeleniuch-Jacquotte, A; Berrino, F; Muti, P; Krogh, AMV; Sieri, S; Pala, V; Venturelli, E; Secreto, G; Barrett-Connor, E; Laughlin, GA; Kabuto, M; Stevens, RG; Neriishi, K; Land, CE; Cauley, JA; Kuller, LH; Helzlsouer, KJ; Alberg, AJ; Bush, TL; Comstock, GW; Gordon, GB; Miller, SR; Longcope, C
2003 DEC ;12(12):1457-1461, Cancer epidemiology biomarkers & prevention
Mathematical methods exist to determine the fractions of sex hormones bound to albumin, bound to sex hormone binding globulin (SHBG), or unbound, using total hormone concentration and SHBG concentration. We used data from eight prospective studies of postmenopausal women to assess the validity of these estimates for fractions of estradiol (E2) and to investigate the impact of using calculated values in breast cancer relative risk (RR) models. Comparisons were made between measured and calculated concentrations of free and non-SHBG-bound E2 in four studies. Relationships between the hormone fractions were investigated and a sensitivity analysis of the calculation performed. Breast cancer RRs were estimated using conditional logistic regression by quintiles of free E2. There is a high correlation (r > 0.91) between calculated and measured values of both free and non-SHBG-bound E2. The calculation is highly sensitive to total hormone concentration but is relatively insensitive to SHBG concentration. In studies with both measured and calculated values, the RRs of breast cancer by quintile of free E2 were almost identical for both estimates; using calculated values in all possible studies the RR in the highest compared with the lowest quintile of free E2 was 2.29 (95% confidence interval, 1.65-3.19). The mathematical method used to calculate fractions of E2 is valid, and RR analyses using calculated values produce similar results to those using measured values. This suggests that for epidemiological studies, it is only necessary to measure total E2 concentration and SHBG concentration, with hormone fractions being obtained by calculation, producing savings in cost, time, and serum
— id: 42543, year: 2003, vol: 12, page: 1457, stat: Journal Article,

Circulating levels of sex steroid hormones and risk of ovarian cancer
Lukanova, Annekatrin; Lundin, Eva; Akhmedkhanov, Arslan; Micheli, Andrea; Rinaldi, Sabina; Zeleniuch-Jacquotte, Anne; Lenner, Per; Muti, Paola; Biessy, Carine; Krogh, Vittorio; Berrino, Franco; Hallmans, Goran; Riboli, Elio; Kaaks, Rudolf; Toniolo, Paolo
2003 May 1;104(5):636-642, International journal of cancer
Experimental and epidemiological evidence supports a role for sex steroid hormones in the pathogenesis of ovarian cancer. We investigated the association between ovarian cancer risk and pre-diagnostic blood concentrations of testosterone, androstenedione, DHEAS, estrone and SHBG. A case-control study nested within 3 cohorts, in New York (USA), Umea (Sweden) and Milan (Italy), included 132 subjects with primary invasive epithelial ovarian cancer. For each case subject, 2 controls were selected who matched a case on cohort, menopausal status, age and date of recruitment and, if premenopausal, day of the menstrual cycle at blood donation. Only women who did not use exogenous hormones at blood donation were included in the study. Conditional logistic regression was used to relate cancer risk to sex steroid hormone concentrations with adjustment for potential confounders. No clear association was observed between ovarian cancer risk and any of the 5 hormones under study. In the premenopausal group, the risk appeared to increase with increasing blood concentrations of androstenedione (upper vs. lower tertile OR = 2.35; 95% CI = 0.81-6.82.), but the small number of subjects in the sub-group precluded reaching unambiguous conclusions about such association. Our study does not support previous observations relating elevations in blood levels of the major sex steroid hormones to an increased risk of ovarian cancer, but offers some evidence that elevated circulating androstenedione before menopause may be associated with increased ovarian cancer risk
— id: 34538, year: 2003, vol: 104, page: 636, stat: Journal Article,

Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy)
Lukanova, Annekatrin; Lundin, Eva; Micheli, Andrea; Akhmedkhanov, Arslan; Rinaldi, Sabina; Muti, Paola; Lenner, Per; Biessy, Carine; Krogh, Vittorio; Riboli, Elio; Hallmans, Goran; Berrino, Franco; Zeleniuch-Jacquotte, Anne; Toniolo, Paolo; Kaaks, Rudolf
2003 Apr;14(3):285-292, Cancer causes & control. ccc
OBJECTIVE: To investigate the association of prediagnostic circulating levels of C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins -1 and -2, as indicators of the biologically active IGF-I concentration, with risk of developing ovarian cancer. METHODS: The study was nested within three prospective cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Case subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed at least one year after blood donation. For each case, two control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. RESULTS: Odds ratios and their 95% confidence intervals for risk of developing ovarian cancer over quartiles of peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66 (0.35-1.23), 0.96 (0.51-1.82) and 0.89 (0.44-1.81) for C-peptide; 1.00, 1.10 (0.58-2.09), 1.07 (0.55-2.04) and 0.79 (0.38-1.62) for IGFBP-1; and 1.00, 1.01 (0.54-1.89), 0.98 (0.51-1.88) and 0.87 (0.45-1.68) for IGFBP-2. In women who had ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1 and IGFBP-2 were 0.51 (0.18-1.49) and 0.53 (0.18-1.54), respectively. CONCLUSIONS: This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55
— id: 44781, year: 2003, vol: 14, page: 285, stat: Journal Article,

Aspirin and lung cancer in women
Akhmedkhanov, A; Toniolo, P; Zeleniuch-Jacquotte, A; Koenig, K L; Shore, R E
2002 Jul 1;87(1):49-53, British journal of cancer
The association between aspirin use and lung cancer risk in women was examined in a case-control study nested in the New York University Women's Health Study, a large cohort in New York. Case subjects were all the 81 incident lung cancer cases who had provided information about aspirin use at enrollment and during the 1994-1996 follow up. Ten controls per case were randomly selected from among study participants who matched a case by age, menopausal status, and dates of enrollment and follow-up. Relative to no aspirin use, the odds ratio for lung cancer (all histological sub-types combined) among subjects who reported aspirin use three or more times per week for at least 6 months was 0.66 (95% confidence interval 0.34-1.28), after adjustment for smoking and education. A stronger inverse association was observed in analyses restricted to non-small cell lung cancer (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.96). These results suggest that regular aspirin use might be inversely associated with risk of lung cancer in women, particularly the non-small cell sub-type
— id: 32489, year: 2002, vol: 87, page: 49, stat: Journal Article,

Characterization of dioxin exposure in residents of Chapaevsk, Russia
Akhmedkhanov, Arslan; Revich, Boris; Adibi, Jennifer J; Zeilert, Vladimir; Masten, Scott A; Patterson, Donald G Jr; Needham, Larry L; Toniolo, Paolo
2002 Nov;12(6):409-417, Journal of exposure analysis & environmental epidemiology
Since 1967, a chemical plant in the town of Chapaevsk (Samara province, Russia) has produced large amounts of chlorinated compounds and is suspected to be a major source of local environmental dioxin contamination. Dioxins have been detected in the local air, soil, drinking water, vegetables, and cow's milk. Human exposure to dioxins is suspected as a factor in the deteriorating local public health. In an effort to characterize nonoccupational dioxin exposure among local residents, during the summer of 1998, 24 volunteers were recruited to donate blood and to provide information about their residence, employment, demographics, medical history, and dietary habits. Selected polychlorinated dibenzodioxins, dibenzofurans, and coplanar biphenyls were measured in blood serum samples. The mean concentration of total dioxin World Health Organization toxic equivalents (WHO-TEQ(98)) based on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) was 61.2 (range 16.4-168.1) pg/g lipid. Subjects living in close proximity to the plant (less than 5 km) had significantly higher dioxin levels (mean WHO-TEQ(98), 75.7 pg/g lipid), as compared to subjects living more than 5 km from the plant (mean WHO-TEQ(98), 44.1 pg/g lipid) (P<0.04). Comparisons of the study results with available published data indicate that average blood dioxin levels were substantially higher in Chapaevsk residents than in nonoccupationally exposed populations of other parts of Russia, Europe, and North America. Chronic exposures of such magnitude may have appreciable adverse effects on public health
— id: 34541, year: 2002, vol: 12, page: 409, stat: Journal Article,

Prospective analysis on the relation of the 677C -> T polymorphism in methylenetetrahydrofolate reductase gene and risk of breast cancer
Chen, J; Akhmedkhanov, A; Toniolo, P; Zhang, S; Willett, W; Hunter, DJ
2002 SEP ;46(6):117-118, International journal of cancer
— id: 32543, year: 2002, vol: 46, page: 117, stat: Journal Article,

Insulin-like growth factor II and colorectal cancer risk in women
Hunt, Kelly J; Toniolo, Paolo; Akhmedkhanov, Arslan; Lukanova, Annekatrin; Dechaud, Henri; Rinaldi, Sabina; Zeleniuch-Jacquotte, Anne; Shore, Roy E; Riboli, Elio; Kaaks, Rudolf
2002 Sep;11(9):901-905, Cancer epidemiology biomarkers & prevention
Recently, a number of prospective studies showed evidence that the growth hormone/insulin-like growth factor I (IGF-I) axis may be important in the development of colorectal cancer. However, only a few studies have reported on the possible relationship of colorectal cancer risk with circulating levels of IGF-II, which are not growth hormone dependent and which do not vary with alterations in energy balance. In a case-control study of 102 cases and 200 matched controls nested within a cohort of 14,275 women in New York, we examined the relationship between colorectal cancer risk and prediagnostic serum levels of IGF-II. Conditional logistic regression analysis showed an odds ratio (OR) for colorectal cancer of 2.02 (95% confidence interval (CI): 0.83-4.93), comparing the upper to lower quintile of IGF-II. This association was slightly attenuated after excluding IGF-II measurements in serum samples taken within 1 year before case diagnosis (OR of 1.81; 95% CI: 0.71-4.64) and moderately attenuated after excluding IGF-II measurements in serum samples taken within 2 years before case diagnosis (OR of 1.47; 95% CI: 0.56-3.91). Adjustment for IGF-1, IGF binding protein (BP)-1, IGFBP-3, smoking, or body mass index did not substantially alter the association, whereas adjustment for IGFBP-2 moderately attenuated the relationship. Our results confirm those of three recent case-control studies, and collectively these results suggest a possible increase in colorectal cancer risk among subjects with comparatively elevated serum IGF-II. Mechanisms that might cause the increase in IGF-II levels are unknown but may include loss of parental imprinting of the IGF-II gene
— id: 34544, year: 2002, vol: 11, page: 901, stat: Journal Article,

Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies
Key, T; Appleby, P; Barnes, I; Reeves, G
2002 Apr 17;94(8):606-616, Journal of the National Cancer Institute
BACKGROUND: Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk. We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women. METHODS: We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not. None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels. The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case-control sets matched within each study. Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate. RESULTS: The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21 (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to 2.71; P(trend)<.001); the RRs for women with increasing quintiles of free estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24 (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The magnitudes of risk associated with the other estrogens and with the androgens were similar. SHBG was associated with a decrease in breast cancer risk (P(trend) =.041). The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis. CONCLUSION: Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women
— id: 38580, year: 2002, vol: 94, page: 606, stat: Journal Article,

Circulating levels of insulin-like growth factor-I and risk of ovarian cancer
Lukanova, Annekatrin; Lundin, Eva; Toniolo, Paolo; Micheli, Andrea; Akhmedkhanov, Arslan; Rinaldi, Sabina; Muti, Paola; Lenner, Per; Biessy, Carine; Krogh, Vittorio; Zeleniuch-Jacquotte, Anne; Berrino, Franco; Hallmans, Goran; Riboli, Elio; Kaaks, Rudolf
2002 Oct 20;101(6):549-554, International journal of cancer
Insulin-like growth factor (IGF)-I, a mitogenic and anti-apoptotic peptide, has been implicated in the development of several cancers. We hypothesized that high circulating IGF-I concentrations may be associated with an increased risk of ovarian cancer. A case-control study was nested within 3 prospective cohorts in New York (USA), Umea (Sweden) and Milan (Italy). One hundred thirty-two women with primary invasive epithelial ovarian cancer diagnosed at least 1 year after blood donation were case subjects. For each case, 2 control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. There was no association between IGF-I concentrations and ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at a young age (<55), circulating IGF-I was directly and strongly associated with ovarian cancer risk (OR = 4.97; 95% CI = 1.22-20.2 for the top vs. the bottom IGF-I tertile after adjustment for parity, BMI categories and smoking). There was no significant association of IGF binding protein-3 with ovarian cancer risk. We found a strong direct relationship between circulating IGF-I levels and risk of developing ovarian cancer before age 55. Additional, larger studies of this association are needed to provide more precise estimates of effect
— id: 34543, year: 2002, vol: 101, page: 549, stat: Journal Article,

Body mass index in relation to ovarian cancer: a multi-centre nested case-control study
Lukanova, Annekatrin; Toniolo, Paolo; Lundin, Eva; Micheli, Andrea; Akhmedkhanov, Arslan; Muti, Paola; Zeleniuch-Jacquotte, Anne; Biessy, Carine; Lenner, Per; Krogh, Vittorio; Berrino, Franco; Hallmans, Goran; Riboli, Elio; Kaaks, Rudolf
2002 Jun 1;99(4):603-608, International journal of cancer
The incidence of ovarian cancer is up to 10 times higher in Western countries than in rural Asia and Africa. One common consequence of a Western lifestyle is the development of excessive body weight and obesity. A multi-centre prospective study was conducted to investigate the association between body mass index (BMI) and ovarian cancer risk. A case-control study was nested within 3 prospective cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Information on anthropometry, demographic characteristics, medical history and lifestyle was obtained at the time of subjects' recruitment in each cohort. Women diagnosed with primary, invasive epithelial ovarian cancer from the 3 cohorts (n = 122) diagnosed 12 months or later after recruitment into the respective cohort served as case subjects. For each case subject, 2 control subjects that matched the case subject on cohort, menopausal status, age and date of recruitment were randomly identified. Data were analyzed by conditional logistic regression. There was an inverse association between BMI and ovarian cancer risk. For increasing quartiles of BMI above the lowest, the ORs were 0.62 (0.32-1.21), 0.59 (0.30-1.17) and 0.46 (0.23-0.92), p = 0.03. Analyses limited to women diagnosed 3 or more years after recruitment into the cohorts did not alter these findings. When obese women (BMI > 30) were compared to lean women (BMI < or = 23), the inverse association became stronger, with an OR of 0.38 (0.17-0.85), p < 0.02. There was some evidence of direct association of ovarian cancer with height, which was limited to cancers diagnosed before age 55. Our data suggest that increasing body weight may confer a protection against ovarian cancer
— id: 34545, year: 2002, vol: 99, page: 603, stat: Journal Article,

Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies
Missmer, Stacey A; Smith-Warner, Stephanie A; Spiegelman, Donna; Yaun, Shiaw-Shyuan; Adami, Hans-Olov; Beeson, W Lawrence; van den Brandt, Piet A; Fraser, Gary E; Freudenheim, Jo L; Goldbohm, R Alexandra; Graham, Saxon; Kushi, Lawrence H; Miller, Anthony B; Potter, John D; Rohan, Thomas E; Speizer, Frank E; Toniolo, Paolo; Willett, Walter C; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Hunter, David J
2002 Feb;31(1):78-85, International journal of epidemiology
BACKGROUND: More than 20 studies have investigated the relation between meat and dairy food consumption and breast cancer risk with conflicting results. Our objective was to evaluate the risk of breast cancer associated with meat and dairy food consumption and to assess whether non-dietary risk factors modify the relation. METHODS: We combined the primary data from eight prospective cohort studies from North America and Western Europe with at least 200 incident breast cancer cases, assessment of usual food and nutrient intakes, and a validation study of the dietary assessment instrument. The pooled database included 351,041 women, 7379 of whom were diagnosed with invasive breast cancer during up to 15 years of follow-up. RESULTS: We found no significant association between intakes of total meat, red meat, white meat, total dairy fluids, or total dairy solids and breast cancer risk. Categorical analyses suggested a J-shaped association for egg consumption where, compared to women who did not eat eggs, breast cancer risk was slightly decreased among women who consumed < 2 eggs per week but slightly increased among women who consumed > or = 1 egg per day. CONCLUSIONS: We found no significant associations between intake of meat or dairy products and risk of breast cancer. An inconsistent relation between egg consumption and risk of breast cancer merits further investigation
— id: 34749, year: 2002, vol: 31, page: 78, stat: Journal Article,

Reliability and validity of direct radioimmunoassays for measurement of postmenopausal serum androgens and estrogens
Rinaldi, S; Dechaud, H; Toniolo, P; Kaaks, R
2002 ;156(5):323-325, IARC scientific publications (Lyon)
— id: 44782, year: 2002, vol: 156, page: 323, stat: Journal Article,

Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations
Rinaldi, Sabina; Geay, Annabelle; Dechaud, Henri; Biessy, Carine; Zeleniuch-Jacquotte, Anne; Akhmedkhanov, Arslan; Shore, Roy E; Riboli, Elio; Toniolo, Paolo; Kaaks, Rudolf
2002 Oct;11(10 Pt 1):1065-1071, Cancer epidemiology biomarkers & prevention
In this study, we validated measurements of free testosterone (fT) and free estradiol (fE(2)) concentrations calculated from total serum concentrations of testosterone (T), estradiol (E(2)), and sex hormone-binding globulin (SHBG), measured by direct, commercial radioimmunoassays, by comparison with reference measurements obtained by dialysis plus an in-house radioimmunoassay after extraction and chromatographic purification. The study was conducted in serum samples from 19 postmenopausal women who were part of an ongoing prospective cohort study. We also performed sensitivity analyses to examine the robustness of the theoretical calculations. Sensitivity analyses showed that in this population, competitive binding of dihydrotestosterone and total T could be ignored in the calculation of fE(2), and competitive binding by dihydrotestosterone does not need to be taken into account for calculation of fT. Furthermore, variations in albumin and SHBG concentrations had negligible effects on fT and fE(2) calculations. Values of fT and fE(2), calculated from total T and E(2) concentrations obtained by the same in-house radioimmunoassay used for the dialysis method, correlated highly with the measurements by dialysis (Pearson's coefficients of correlation above 0.97). When calculating fT and fE(2) using total T and total E(2) concentrations obtained by different direct radioimmunoassays, almost all kits gave good correlations with the reference method for fT (Pearson's r > 0.83), but only a few gave good correlations for fE(2) (Diagnostic System Laboratories and DiaSorin; r > 0.80). The direct radioimmunoassays giving the best correlation for fT and fE(2) with the dialysis method were those that best measured total concentrations of T and E(2). Furthermore, mean values of fT and fE(2) corresponded well to mean values by the reference method if SHBG measurements were also well calibrated. We conclude that in postmenopausal women, theoretical calculations are valid for the determination of fT and fE(2) concentrations and can give reliable estimation of cancer risk in epidemiological studies when the total concentrations of T, E(2), and SHBG are measured accurately
— id: 34542, year: 2002, vol: 11, page: 1065, stat: Journal Article,

Serum fatty acids and risk of breast cancer in a nested case-control study of the New York University Women's Health Study
Saadatian-Elahi, M; Toniolo, P; Ferrari, P; Goudable, J; Akhmedkhanov, A; Zeleniuch-Jacquotte, A; Riboli, E
2002 ;156(5):227-230, IARC scientific publications (Lyon)
— id: 34539, year: 2002, vol: 156, page: 227, stat: Journal Article,

Serum fatty acids and risk of breast cancer in a nested case-control study of the New York University Women's Health Study
Saadatian-Elahi, Mitra; Toniolo, Paolo; Ferrari, Pietro; Goudable, Joelle; Akhmedkhanov, Arslan; Zeleniuch-Jacquotte, Anne; Riboli, Elio
2002 Nov;11(11):1353-1360, Cancer epidemiology biomarkers & prevention
Migrant and experimental animal studies suggest that differences in breast cancer incidence rates may be related, in part, to intake of dietary fat. The experimental evidence indicates that total fat, saturated, and n-6 polyunsaturated fatty acids (PUFAs) may stimulate both mammary tumor growth and metastasis, whereas n-3 PUFAs may have a tumor-inhibiting effect. Overall, epidemiological studies do not appear to confirm such observations. Within a cohort of women in the New York University Women's Health Study, the fatty acid composition of serum phospholipids was analyzed by gas chromatography among 197 pre- and postmenopausal clinically identified breast cancer subjects and their matched controls. Individual fatty acids in serum phospholipids were expressed as a percentage of total fatty acids. No significant difference was observed in the proportion of saturated fatty acids (SFAs), monounsaturated fatty acids, or n-6 and n-3 PUFAs between cases and controls. After menopause, total SFAs were positively associated with the risk of breast cancer [odds ratio (OR) = 1.96, 95% confidence interval (CI): 0.73-5.25; P = 0.05] after adjustment for potential confounding factors. Myristc acid (C14:0) was suggestive of a small increase in breast cancer risk in premenopausal women (OR = 2.22, 95% CI: 0.78-6.31), whereas palmitic acid (C16:0) showed similar trends in postmenopausal women (OR = 2.57, 95% CI: 0.99-6.61). Overall, total PUFAs (n-6 and n-3) were suggestive of a small protective effect (OR = 0.59, 95% CI: 0.31-1.09). No significant associations were found between other fatty acids and the risk of breast cancer. The study suggested evidence of an association between serum levels of SFAs and the risk of breast cancer in postmenopausal women. Neither individual n-3 fatty acids of marine origin, eicosapentaenoic acid (C20:5 n-3), and docosahexaenoic acid (C22:6 n-3), nor n-6 PUFAs were related to cancer risk in this study
— id: 34540, year: 2002, vol: 11, page: 1353, stat: Journal Article,

Aspirin and epithelial ovarian cancer
Akhmedkhanov A; Toniolo P; Zeleniuch-Jacquotte A; Kato I; Koenig KL; Shore RE
2001 Dec;33(6):682-687, Preventive medicine
BACKGROUND: Epidemiological evidence suggests that chronic inflammation may influence ovarian carcinogenesis. The study objective was to examine the association between the commonly used anti-inflammatory drug aspirin and epithelial ovarian cancer. METHODS: The authors conducted a case-control study based in the New York University Women's Health Study cohort enrolled between 1985 and 1991 in New York City. After a median follow-up period of 12 years, 68 incident cases of epithelial ovarian cancer were identified. Data about regular aspirin use were collected during the 1994-1996 follow-up questionnaire. Using a case-control study design, 10 controls per case were randomly selected among study participants who matched the case by age and menopausal status. Conditional logistic regression analysis was used to study the relationships between aspirin and epithelial ovarian cancer by generating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Relative to no aspirin use, the OR for epithelial ovarian cancer among women who reported aspirin use three or more times per week for a period of at least 6 months was 0.60 (95% CI 0.26, 1.38), after adjustment for age at menarche, parity, oral contraceptive use, and first-degree family history of breast cancer before age 50. Among recent, within the previous 5 years, users of aspirin, the adjusted OR was 0.36 (95% CI 0.11, 1.18). CONCLUSION: Although confidence intervals included unity, the observed risk estimates seem to be compatible with previous studies suggesting that regular aspirin use could be inversely associated with risk of epithelial ovarian cancer
— id: 26517, year: 2001, vol: 33, page: 682, stat: Journal Article,

Luteinizing hormone, its beta-subunit variant, and epithelial ovarian cancer: the gonadotropin hypothesis revisited
Akhmedkhanov A; Toniolo P; Zeleniuch-Jacquotte A; Pettersson KS; Huhtaniemi IT
2001 Jul 1;154(1):43-49, American journal of epidemiology
The gonadotropin hypothesis postulates that excessive gonadotropin stimulation results in increased proliferation and subsequent malignant transformation of ovarian epithelium. The authors evaluated this hypothesis by analyzing the association between serum levels of wild-type luteinizing hormone (LH) and ovarian cancer risk. They also examined the relation between a variant of LH containing two missense point mutations (Trp(8)Arg and Ile(15)Thr) in its beta-subunit and ovarian cancer risk. Fifty-eight cases of epithelial ovarian cancer and 116 controls matched on age, menopausal status, and date of blood donation were included in a case-control study nested within the New York University Women's Health Study, a prospective cohort enrolled between 1985 and 1991 in New York City. Wild-type serum levels and variant LH status were determined by immunofluorometric assays in which monoclonal antibodies specific for wild-type and variant LH were used. Compared with women in the lowest tertile of wild-type LH, women in the highest tertile had a lower risk of ovarian cancer, after adjustment for potential confounders (odds ratio = 0.42, 95% confidence interval: 0.09, 2.09). Women heterozygous for variant LH were not at increased risk (adjusted odds ratio = 0.95, 95% confidence interval: 0.27, 3.34). The results suggest that neither wild-type LH levels nor variant LH status is associated with increased risk of epithelial ovarian cancer
— id: 21164, year: 2001, vol: 154, page: 43, stat: Journal Article,

Role of exogenous and endogenous hormones in endometrial cancer: review of the evidence and research perspectives
Akhmedkhanov A; Zeleniuch-Jacquotte A; Toniolo P
2001 Sep;943(3):296-315, Annals of the New York Academy of Sciences
Endometrial carcinoma is the most common cancer of the female reproductive organs in the United States. International comparisons reveal that the incidence of endometrial cancer vary widely between different countries with the highest rates observed in North America and Northern Europe, intermediate rates in Eastern Europe and Latin America, and lowest rates in Asia and Africa. International variation in endometrial cancer rates may represent differences in the distribution of known risk factors, which include obesity, postmenopausal estrogen replacement, ovarian dysfunction, diabetes mellitus, infertility, nulliparity, and tamoxifen use. Most of the risk factors for endometrial cancer can be explained within the framework of the unopposed estrogen hypothesis, which proposes that exposure to estrogens unopposed by progesterone or synthetic progestins leads to increased mitotic activity of endometrial cells, increased number of DNA replication errors, and somatic mutations resulting in malignant phenotype. Although the impact of exogenous hormone replacement was intensively studied during the last two decades, less is known about the effects of endogenous hormones in endometrial cancer. A review of available experimental, clinical, and epidemiologic data suggests that in addition to estrogens, other endogenous hormones, including progesterone, androgens, gonadotropins, prolactin, insulin, and insulin-like growth factors, may play a role in the pathogenesis of different histopathologic types of endometrial cancer
— id: 26645, year: 2001, vol: 943, page: 296, stat: Journal Article,

Changes in self-reported family history of breast cancer with change in case-control status
Garbers V; Toniolo PG; Taioli E
2001 ;17(6):517-520, European journal of epidemiology
In order to study recall bias in self-reported family history of breast cancer, we selected a sample of cases and controls from a case-control study nested in a cohort, and compared family history reported in a questionnaire at enrollment, and after the development of the disease. We assessed whether changes occurred in self-reported familial breast cancer due to a change in health status in women who developed breast cancer. The kappa of agreement for maternal history of breast cancer was 0.92 in cases, and 1.00 in controls; the kappa for history of breast cancer in sisters was 0.65 in cases, 0.88 in controls. By comparing two questionnaires collected before the diagnosis of the cases (index date), and one questionnaire administered after the index date, we were able to assess that the changes in answer observed among the cases were recorded in the second questionnaire before the index date, and therefore were independent from the diagnosis of cancer. The study seems to suggest that change in recall is of limited importance when collecting family history of first degree relatives, and that women recall the health history of their mother better than the health history of their sisters
— id: 35805, year: 2001, vol: 17, page: 517, stat: Journal Article,

Correspondence re: Giovannucci et al., A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol. Biomark. Prev., 9: 345-349, 2000
Kaaks R; Rinaldi S; Lukanova A; Akhmedkhanov A; Zeleniuch-Jacquotte A; Toniolo P
2001 Oct;10(10):1103-1104, Cancer epidemiology biomarkers & prevention
— id: 34547, year: 2001, vol: 10, page: 1103, stat: Journal Article,

A prospective study of insulin-like growth factor-I, IGF-binding proteins-1, -2 and -3 and lung cancer risk in women
Lukanova A; Toniolo P; Akhmedkhanov A; Biessy C; Haley NJ; Shore RE; Riboli E; Rinaldi S; Kaaks R
2001 Jun 15;92(6):888-892, International journal of cancer
Insulin-like growth factor-I (IGF-I) has mitogenic and anti-apoptotic properties and has been implicated in the development of breast, colorectum, prostate and lung cancer. IGF binding proteins (IGFBPs) are not only carrier proteins for IGFs but also hold a central position in IGF ligand-receptor interactions through influences on the bioavailability and distribution of IGFs in the extracellular environment. A case-control study nested within the New York University Women's Health Study Cohort included 93 women diagnosed with lung cancer at least 6 months after recruitment into the study. Two controls (n = 186) were matched to each case on age, date of blood sampling, menopausal status, day of menstrual cycle and questionnaire data of smoking status at the time of blood donation. Serum IGF-I, IGFBP-1, -2 and -3, insulin and cotinine were measured. Mean serum levels of IGF-I, IGFBP-1, -2 and -3 were not significantly different between the case and control groups. Univariate logistic regression analyses showed no association of lung cancer risk with serum levels of IGF-I or any of the IGFBPs. These results remained virtually the same in multivariate analyses, including adjustment for cotinine, time since last meal, BMI, IGF-I or IGFBP-3, respectively. Exclusion of cases diagnosed within 3 years of recruitment in the cohort, or restriction of the analyses to adenocarcinomas only, did not alter these results. Our study does not offer evidence in support of an association between prediagnostic serum levels of IGF-I or IGFBP-1, -2 and -3 and lung cancer risk in women
— id: 34549, year: 2001, vol: 92, page: 888, stat: Journal Article,

A cross-sectional study of IGF-I determinants in women
Lukanova A; Toniolo P; Akhmedkhanov A; Hunt K; Rinaldi S; Zeleniuch-Jacquotte A; Haley NJ; Riboli E; Stattin P; Lundin E; Kaaks R
2001 Oct;10(5):443-452, European journal of cancer prevention
Evidence is accumulating that elevated circulating insulin-like growth factor I (IGF-I) is related to increased cancer risk. The identification of hormonal, reproductive and lifestyle characteristics influencing its synthesis and bioavailability is of particular interest. Data from 400 women, who served as controls in two case-control studies nested within the same prospective cohort study, were combined. IGF-I, IGF-binding proteins 1, 2 and 3 (IGFBP-1, -2, -3) and insulin were measured in serum samples from all subjects and cotinine in 186 samples. Age appears to be the most important determinant of total IGF-I levels in women. Anthropometric measures, such as body mass index (BMI) or waist-to-hip ratio (WHR) do not seem to influence total IGF-I concentrations in peripheral blood, but may modulate IGF-I bioavailability through insulin-dependent changes in IGFBP-1 and -2 concentrations. Age at menarche, phase of the menstrual cycle at blood draw, parity, menopause, past oral contraceptive or hormone replacement therapy use, and tobacco smoking do not appear to exert an independent effect on IGF-I and its binding proteins. There was some suggestion that regular physical activity may increase total IGF-I and that women with positive family history of breast cancer might have higher IGF-I levels than those without such diagnosis in their relatives
— id: 34546, year: 2001, vol: 10, page: 443, stat: Journal Article,

Reliability and validity of commercially available, direct radioimmunoassays for measurement of blood androgens and estrogens in postmenopausal women
Rinaldi S; Dechaud H; Biessy C; Morin-Raverot V; Toniolo P; Zeleniuch-Jacquotte A; Akhmedkhanov A; Shore RE; Secreto G; Ciampi A; Riboli E; Kaaks R
2001 Jul;10(7):757-765, Cancer epidemiology biomarkers & prevention
In large-scale epidemiological studies on endogenous sex steroids and cancer risk, direct immunoassays of circulating hormone levels have the advantage of being fast and comparatively inexpensive while requiring only small sample volumes. On the other hand, indirect assays after organic extraction and chromatographic prepurification have the advantage of reducing specific interferences and matrix effects and hence are thought to have better validity. We compared direct assays of testosterone (T, six different assays), Delta4-androstenedione (A, four assays), estrone (E(1), one assay), and 17beta-estradiol (E(2), five assays) with measurements obtained by an indirect assay in a representative subset of 20 postmenopausal women who were part of a large prospective cohort study. Within-batch reproducibilities of the subject rankings by relative hormone levels were good (intraclass correlations >0.89) for all direct assays tested. Between batches, reproducibilities generally were also acceptable (r > 0.80) to good (r > 0.90) in terms of Pearson's correlations. The between-batch reproducibility in terms of intraclass correlations was systematically lower in terms of Pearson's correlations, however, because of between-batch variations in the absolute scale of measurements. The relative validity of direct versus indirect assays in terms of the subjects' ranking by relative hormone levels was also high for most of the kits tested for T, A, and E(1) (Pearson's correlations between 0.70 and 0.89) but was high for only two kits of five tested for E(2) (correlations of 0.86 and 0.84). On an absolute scale, mean measurement values were generally higher for direct assays than for the indirect assay and, for each hormone, varied substantially, depending on the kit used. Overall, the results of this study show that, with careful selection, commercial kits for direct radioimmunoassays of steroid hormones in postmenopausal serum can be found that may allow a reliable estimation of relative risks in epidemiological studies. However, standardization of the absolute scale of assays remains problematic
— id: 34548, year: 2001, vol: 10, page: 757, stat: Journal Article,

Types of dietary fat and breast cancer: a pooled analysis of cohort studies
Smith-Warner SA; Spiegelman D; Adami HO; Beeson WL; van den Brandt PA; Folsom AR; Fraser GE; Freudenheim JL; Goldbohm RA; Graham S; Kushi LH; Miller AB; Rohan TE; Speizer FE; Toniolo P; Willett WC; Wolk A; Zeleniuch-Jacquotte A; Hunter DJ
2001 Jun 1;92(5):767-774, International journal of cancer
Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption
— id: 34751, year: 2001, vol: 92, page: 767, stat: Journal Article,

Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies
Smith-Warner SA; Spiegelman D; Yaun SS; Adami HO; Beeson WL; van den Brandt PA; Folsom AR; Fraser GE; Freudenheim JL; Goldbohm RA; Graham S; Miller AB; Potter JD; Rohan TE; Speizer FE; Toniolo P; Willett WC; Wolk A; Zeleniuch-Jacquotte A; Hunter DJ
2001 Feb 14;285(6):769-776, JAMA
CONTEXT: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. OBJECTIVE: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. DATA SOURCES/STUDY SELECTION: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. DATA EXTRACTION: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. DATA SYNTHESIS: The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend =.08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend =.54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend =.12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. CONCLUSION: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk
— id: 34752, year: 2001, vol: 285, page: 769, stat: Journal Article,

Serum carotenoids and breast cancer
Toniolo P; Van Kappel AL; Akhmedkhanov A; Ferrari P; Kato I; Shore RE; Riboli E
2001 Jun 15;153(12):1142-1147, American journal of epidemiology
The consumption of vegetables and fruit may protect against many types of cancer, but research evidence is not compelling for breast cancer. Carotenoids are pigments that are present in most plants and have known antioxidant properties. Blood concentrations of carotenoids have been proposed as integrated biochemical markers of vegetable, fruit, and synthetic supplements consumed. In a case-control study (270 cases, 270 controls) nested within a cohort in New York during 1985-1994, the carotenoids lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene were measured in archived serum samples using liquid chromatography. There was an evident increase in the risk of breast cancer for decreasing beta-carotene, lutein, alpha-carotene, and beta-cryptoxanthin. The risk of breast cancer approximately doubled among subjects with blood levels of beta-carotene at the lowest quartile, as compared with those at the highest quartile (odds ratio = 2.21; 95% confidence interval (CI): 1.29, 3.79). The risk associated with the other carotenoids was similar, varying between 2.08 (95% CI: 1.11, 3.90) for lutein and 1.68 (95% CI: 0.99, 2.86) for beta-cryptoxanthin. The odds ratio for the lower quartile of total carotenoids was 2.31 (95% CI: 1.35, 3.96). These observations offer evidence that a low intake of carotenoids, through poor diet and/or lack of vitamin supplementation, may be associated with increased risk of breast cancer and may have public health relevance for people with markedly low intakes
— id: 21175, year: 2001, vol: 153, page: 1142, stat: Journal Article,

"Toniolo and Akhmedkhanov respond to ""serum carotenoids and breast cancer"" by Rohan"
Toniolo, P; Akhmedkhanov, A
2001 JUN 15 ;153(12):1151-1151, American journal of epidemiology
— id: 55043, year: 2001, vol: 153, page: 1151, stat: Journal Article,

Serum carotenoids as biomarkers of fruit and vegetable consumption in the New York Women's Health Study
van Kappel AL; Steghens JP; Zeleniuch-Jacquotte A; Chajes V; Toniolo P; Riboli E
2001 Jun;4(3):829-835, Public health nutrition
OBJECTIVE: To investigate the usefulness of serum carotenoids as biomarkers of fruit and vegetable consumption. DESIGN:: Reproducibility study on three repeat measurements of serum carotenoids. Correlation analysis of carotenoids and dietary food intake, and regression analysis of potential predictive parameters for serum carotenoid levels. SETTING: New York, USA. SUBJECT:: Women participating in the New York Women's Health Study, a prospective study of sex hormones, diet and breast cancer. Forty-eight women with three repeat blood samples and 302 women having a blood sample and a dietary history questionnaire (including 47 subjects from the reproducibility study). RESULTS: Serum carotenoid concentrations were highly reproducible between one- and two-year repeat samples. Estimated fruit and vegetable consumption was positively correlated with serum carotenoid concentrations but correlation coefficients were low. Consumption of fruit was predictive for serum levels of beta-carotene, alpha-carotene and beta-cryptoxanthin, while vegetable consumption was predictive for serum beta-carotene, lutein, zeaxanthin and lycopene. Serum concentrations of cholesterol and triglycerides were predictive for serum carotenoids but adjustment for their levels had little or no influence on the correlation between fruit and vegetable consumption and serum carotenoid concentrations. CONCLUSIONS: One single serum measurement of alpha-carotene, beta-carotene and lutein can accurately rank subjects according to their usual serum level. Serum concentrations, however, correlate only moderately with estimated dietary intake of fruits or vegetables and should therefore be used with caution as biomarkers of fruit and vegetable intake
— id: 34750, year: 2001, vol: 4, page: 829, stat: Journal Article,

Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study
Zeleniuch-Jacquotte A; Akhmedkhanov A; Kato I; Koenig KL; Shore RE; Kim MY; Levitz M; Mittal KR; Raju U; Banerjee S; Toniolo P
2001 Apr 6;84(7):975-981, British journal of cancer
We assessed the association of postmenopausal serum levels of oestrogens and sex hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control study nested within the NYU Women's Health Study cohort. Among 7054 women postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a median of 5.5 years after blood donation. Each case was compared to 4 controls matched on age, menopausal status at enrolment, and serum storage duration. Endometrial cancer risk increased with higher levels of oestradiol (odds ratio = 2.4 in highest vs lowest tertile, P for trend = 0.02), percent free oestradiol (OR = 3.5, P< 0.001), and oestrone (OR = 3.9, P< 0.001). Risk decreased with higher levels of percent SHBG-bound oestradiol (OR = 0.43, P = 0.03) and SHBG (OR = 0.39, P = 0.01). Trends remained in the same directions after adjusting for height and body mass index. A positive association of body mass index with risk was substantially reduced after adjusting for oestrone level. Our results indicate that risk of endometrial cancer increases with increasing postmenopausal oestrogen levels but do not provide strong support for a role of body mass index independent of its effect on oestrogen levels.
— id: 21217, year: 2001, vol: 84, page: 975, stat: Journal Article,

Genetic variant of luteinizing hormone and risk of breast cancer in older women [In Process Citation]
Akhmedkhanov A; Toniolo P; Zeleniuch-Jacquotte A; Pettersson K; Huhtaniemi I
2000 Aug;9(8):839-842, Cancer epidemiology biomarkers & prevention
A genetic variant of luteinizing hormone (LH) characterized by two point mutations in codons 8 (TGG-->CGG) and 15 (ATC-->ACC) of the LH beta-subunit gene has been described recently. As compared with wild-type LH, the variant LH appears to have higher in vitro bioactivity but a shortened circulatory half-life, and it has been reported to affect circulating levels of sex hormones. Our purpose was to determine whether the variant form of LH is associated with an altered risk of breast cancer. This hypothesis was addressed in a case-control study nested within a prospective cohort that included 270 cases of breast cancer and twice as many matching control subjects. The study was limited to subjects diagnosed at age 50 years or older. The LH status was determined by the combination of two immunofluorometric assays of serum using monoclonal antibodies. Frequency of the variant LH was similar in breast cancer cases and controls (11.5% versus 10.7%). In conditional regression models, the presence of the variant LH was not associated with a considerable increase of breast cancer risk (odds ratio, 1.07; 95% confidence interval, 0.68-1.69). Adjustment for potential confounders did not notably change the risk estimate (odds ratio, 1.11; 95% confidence interval, 0.69-1.78). These observations do not appear to support the hypothesis that this particular variant of LH is associated with altered risk of breast cancer diagnosed at age 50 years and older
— id: 11536, year: 2000, vol: 9, page: 839, stat: Journal Article,

Maternal pregnancy hormone profiles in areas with a different incidence of breast cancer
Akhmedkhanov AA; Zhu L; Toniolo PG
2000 Nov;83(9):1255-1256, British journal of cancer
— id: 34551, year: 2000, vol: 83, page: 1255, stat: Journal Article,

Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women
Kaaks R; Toniolo P; Akhmedkhanov A; Lukanova A; Biessy C; Dechaud H; Rinaldi S; Zeleniuch-Jacquotte A; Shore RE; Riboli E
2000 Oct 4;92(19):1592-1600, Journal of the National Cancer Institute
BACKGROUND: Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York. METHODS: We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided. RESULTS: Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]). CONCLUSIONS: Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I
— id: 34552, year: 2000, vol: 92, page: 1592, stat: Journal Article,

Risk of iron overload among middle-aged women
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
2000 May;70(3):119-125, International journal for vitamin & nutrition research
Iron overload, expressed as increased body iron stores, has been recognized as a potential hazard because it promotes the generation of oxygen radicals. We analyzed factors associated with serum ferritin levels (an indicator of body iron stores) among middle-aged women with a high prevalence of nutrient supplement use. Serum ferritin concentrations were determined on automated immunoassay for 487 healthy women with the mean age of 57 years who participated in the New York University Women's Health Study. The mean serum ferritin concentration in postmenopausal women was more than twice that in premenopausal women. Serum ferritin concentrations progressively increased with advancing age, but adjustment for menopausal status considerably weakened this association. Among non-dietary factors, nonwhite ethnicity, obesity and cigarette smoking were positively associated with serum ferritin concentrations. After adjustment for these factors and for menopausal status, serum ferritin levels were positively associated with meat intake and multivitamin use and inversely associated with breakfast cereal consumption. However, none of these lifestyle factors positively associated with serum ferritin levels had a significant impact on serum ferritin levels above 100 ng/ml (approximately equal to median concentration). Our results suggest that iron overload seems unlikely among middle aged women through their diet and nutritional supplements
— id: 34554, year: 2000, vol: 70, page: 119, stat: Journal Article,

Diet, smoking and anthropometric indices and postmenopausal bone fractures: a prospective study
Kato I; Toniolo P; Zeleniuch-Jacquotte A; Shore RE; Koenig KL; Akhmedkhanov A; Riboli E
2000 Feb;29(1):85-92, International journal of epidemiology
OBJECTIVE: Bone fractures are an important cause of morbidity and mortality among the elderly in the US. The present study assesses the possible role of a number of risk factors for postmenopausal bone fractures. METHODS: We analysed the relationships of anthropometric, demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospective cohort study, the New York University Women's Health Study. RESULTS: After an average of 7.6 years of follow-up, 1025 new incident bone fractures were reported, including 34 hip and 159 wrist fractures (incidence rates; 71.6 and 334.7 per 105 woman-years, respectively). The risk of fracture increased with increasing age, body height and total fat intake, while it was significantly lower among obese and African American women. The relative risk among African Americans was 0.45 (95% CI: 0.32-0.63) compared with non-African Americans. Women taller than 170 cm had a 64% increase in risk of fractures, as compared with those under 155 cm. These associations were generally more pronounced when fractures were limited to those at the hip and wrist. CONCLUSIONS: The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity, short stature and African American ethnicity
— id: 10348, year: 2000, vol: 29, page: 85, stat: Journal Article,

Psychotropic medication use and risk of hormone-related cancers: the New York University Women's Health Study
Kato I; Zeleniuch-Jacquotte A; Toniolo PG; Akhmedkhanov A; Koenig K; Shore RE
2000 Jun;22(2):155-160, Journal of public health medicine
BACKGROUND: The use of psychotropic medications may increase the risk of hormone-related cancers in females through increased gonadotropin secretion, but the data from epidemiologic studies are limited to evaluate the hypothesis. METHODS: The association between the use of psychotropic medications and cancer incidence was studied in a prospective cohort study that involves 15,270 women who participated in mammographic screening. The relative risks (RR) and 95 per cent confidence intervals (CIs) for cancer associated with the use of psychotropic medications were estimated by the Cox's proportional hazard model. RESULTS: During an average of 7.3 years of follow-up, 1,130 incident cases of cancer were identified, including 566 breast, 67 endometrial and 47 ovarian cancers. The use of any type of psychotropic medication at baseline was associated with increased risks of breast [relative risk (RR) = 1.39, 95 per cent CI 1.11-1.74], endometrial (RR=1.71; 95 per cent CI 0.93-3.14) and ovarian (RR= 1.48, 95 per cent CI 0.69-3.16) cancers, whereas no increase in risk was observed for other cancers (RR = 1.06). When the subjects were divided by menopausal status at baseline, premenopausal women tended to have higher risk of all hormone-related cancers (RR = 1.73, 95 per cent CI 1.27-2.35) than postmenopausal women (RR=1.23, 95 per cent CI 0.94-1.62). The magnitude of the RR associated with the use of these medications did not change by length of follow-up. Analysis by type of medication did not find that the association was limited to specific types. CONCLUSION: The observed association needs to be confirmed in further studies based on more detailed medication history
— id: 34553, year: 2000, vol: 22, page: 155, stat: Journal Article,

Serum insulin-like growth factor-I and breast cancer
Toniolo P; Bruning PF; Akhmedkhanov A; Bonfrer JM; Koenig KL; Lukanova A; Shore RE; Zeleniuch-Jacquotte A
2000 Dec 1;88(5):828-832, International journal of cancer
Insulin-like growth factor I (IGF-I) is a systemic hormone with potent mitogenic and anti-apoptotic properties, which could influence the proliferative behavior of normal breast cells. Limited epidemiological observations suggest that the hormone may play a role in the etiology of breast cancer, especially at pre-menopausal ages. In a prospective case-control study nested within a cohort of New York City women, IGF-I, IGF-binding protein 3 (IGFBP-3) and C peptide were measured in frozen serum samples from 172 pre-menopausal and 115 post-menopausal subjects who were subsequently diagnosed with breast cancer. Subjects were eligible if diagnosed 6 months or more after recruitment into the study (7 to 120 months). Cohort members who matched the cases on age, menopausal status, date of blood sampling and day of menstrual cycle at blood collection served as controls. Post-menopausal breast cancer was not associated with serum IGF-I, IGFBP-3 or C-peptide levels. However, the risk of breast cancer increased with increasing serum concentrations of IGF-I in pre-menopausal women. The odds ratio (OR) for the highest quartile of IGF-I (>256 ng/ml) compared to the lowest (<168 ng/ml) was 1.60 [95% confidence interval (CI) 0.91-2. 81]. The OR decreased to 1.49 (95% CI 0.80-2.79) after adjustment for IGFBP-3. In analyses restricted to subjects who were pre-menopausal at the time of blood sampling and whose cancer was diagnosed before age 50, the top vs. bottom quartile OR increased appreciably to 2.30 (95% CI 1.07-4.94). Adjustment for IGFBP-3 reduced the OR to 1.90 (95% CI 0.82-4.42). There was no association between pre-menopausal breast cancer and IGFBP-3, IGF-I:IGFBP-3 ratio or non-fasting levels of C peptide. Elevated circulating levels of IGF-I may be an indicator of increased risk of breast cancer occurring before age 50
— id: 34550, year: 2000, vol: 88, page: 828, stat: Journal Article,

Risk of breast cancer and organochlorine exposure
Wolff MS; Zeleniuch-Jacquotte A; Dubin N; Toniolo P
2000 Mar;9(3):271-277, Cancer epidemiology biomarkers & prevention
A prospective investigation of breast cancer and organochlorine (OC) exposures was undertaken in the New York University Women's Health Study. Cases (n = 148) and individually matched controls (n = 295) were identified among women whose blood had been obtained 6 months or more prior to breast cancer diagnosis. In addition, among 84 cases and 196 controls, two or more consecutive annual blood samples were available to estimate half-lives of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethene (DDE) and polychlorinated biphenyls (PCBs). Cases and controls had similar levels of DDE (geometric mean, 6.95 versus 7.27 ng/ml; lipid-adjusted geometric mean, 977 versus 1100 ng/g) and PCBs (5.04 versus 4.97 ng/ml; lipid-adjusted geometric mean, 683 versus 663 ng/g). These differences remained nonsignificant when estrogen receptor status of tumors was considered. DDE and PCB half-lives did not differ in case versus control patients. In control patients, DDE and PCB half-lives were strongly correlated (r(s) = 0.71), and the half-life of DDE (but not that of PCB) was inversely correlated with body mass index (BMI), yet the blood serum levels of PCB (but not those of DDE) were correlated with BMI. We conclude that there is no evidence for an association of breast cancer risk with DDE or PCB levels in blood (based on samples collected during the period 1987-1992) nor with their elimination half-lives. However, changes in DDE and PCBs over time are influenced by metabolism, BMI, and current OC exposures, and each may affect interpretation of OC levels in risk assessment models
— id: 34754, year: 2000, vol: 9, page: 271, stat: Journal Article,

Reliability of fatty acid composition in human serum phospholipids
Zeleniuch-Jacquotte A; Chajes V; Van Kappel AL; Riboli E; Toniolo P
2000 May;54(5):367-372, European journal of clinical nutrition
OBJECTIVE: We examined the reliability of the fatty acid composition of serum phospholipids in the New York University Women's Health Study, a prospective study of sex hormones, diet and breast cancer. DESIGN: Non-fasting serum samples collected at three yearly visits, in 46 healthy women, and stored at -80 degrees C for 7-12 y, were included in the study. Serum phospholipid fatty acid composition was measured by capillary gas chromatography. RESULTS: For the 20 individual fatty acids measured, the reliability coefficients were less than 0.50 for four, between 0.50 and 0.70 for nine, and greater than 0.70 for seven. Among the major fatty acids, arachidonic and alpha-linolenic acids had high reliability coefficients (0.71 and 0. 72, respectively), palmitic, oleic, linoleic, eicosapentaenoic and docosahexaenoic acids had intermediate coefficients (0.57, 0.69, 0. 62, 0.64 and 0.66, respectively), whereas stearic acid had the lowest coefficient (0.15). The reliability coefficients for total monounsaturated fats, omega-6 and omega-3 fatty acids were moderately high (0.66, 0.53 and 0.66, respectively), whereas the coefficients for total saturated fats and total polyunsaturated fats were low (0.31 and 0.43, respectively). CONCLUSIONS: These results indicate that the fatty acid composition of serum phospholipids can be a useful tool in epidemiologic studies, although for most fatty acids a single determination is associated with some error in measurement that should be taken into account at the design and analysis stages. Storage for up to 12 y at -80 degrees C preserved polyunsaturated fatty acids from oxidation very well
— id: 10347, year: 2000, vol: 54, page: 367, stat: Journal Article,

Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Akhmedkhanov A; Zeleniuch-Jacquotte A; Riboli E
1999 Apr;79(11-12):1917-1922, British journal of cancer
Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case-control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92-4.29). The potentially protective effects of folate need to be confirmed in clinical trials
— id: 6090, year: 1999, vol: 79, page: 1917, stat: Journal Article,

Epidemiologic correlates of serum folate and homocysteine levels among users and non-users of vitamin supplement
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
1999 Sep;69(5):322-329, International journal for vitamin & nutrition research
Lower serum folate and higher serum homocysteine levels are known risk factors for various conditions. Thus, epidemiologic correlates with these measurements were studied for 256 multivitamin users and 230 non-users who were middle-aged women. Both serum folate and homocysteine levels increased with advancing age in both multivitamin users (P < 0.01 and P < 0.01) and non-users (P = 0.08 and P < 0.01). Among non-users, higher intake of vegetables, fruits, cold cereals and total protein were associated positively with serum folate and inversely with homocysteine levels. There were 25-74% increases in serum folate and 10-15% decreases in serum homocysteine between 1st and 4th quartiles of intake of these food/nutrients. In addition, 26% lower serum folate and 18% higher serum homocysteine were observed for those smoking 20 or more cigarettes per day compared with non-smokers. Among multivitamin users, body weight was correlated inversely with serum folate (P < 0.01) and positively with serum homocysteine levels (P = 0.04), while no correlates were found among lifestyle factors. Regular use of multivitamins increased serum folate about fourfold and decreased homocysteine twofold. These results suggest that multivitamin use can offset the effects of an unhealthy lifestyle on these serum markers, and that levels of serum folate and homocysteine can also be favorably influenced by healthier diet and abstinence from smoking
— id: 6221, year: 1999, vol: 69, page: 322, stat: Journal Article,

Iron intake, body iron stores and colorectal cancer risk in women: a nested case-control study
Kato I; Dnistrian AM; Schwartz M; Toniolo P; Koenig K; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
1999 Mar 1;80(5):693-698, International journal of cancer
Accumulated evidence suggests that increased body iron stores may increase the risk of colorectal cancer, possibly via catalyzing oxidation reactions. We examined the relationship between iron status and colorectal cancer in a case-control study nested within the New York University Women's Health Study cohort. For 105 incident cases of colorectal cancer with an average follow-up of 4.7 years and 523 individually matched controls, baseline levels of serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation were determined as indicators of body iron stores, and total iron intake was assessed based on their diet and supplement intake. Overall, there were no associations between the risk of colorectal cancer and any of these indices except for serum ferritin, which showed a significant inverse association. When analyzed by subsite, there was an increasing trend in risk of cancer of the proximal colon with increasing total iron intake (p-value for trend = 0.04). In addition, a significantly increased risk of colorectal cancer associated with higher total iron intake [odds ratio (OR) = 2.50; 95% confidence interval (CI): 1.06-5.87] was observed among subjects with higher intake of total fat. Our results do not support a role of increased body iron stores in the development of colorectal cancer, but suggest that luminal exposure to excessive iron may possibly increase the risk in combination with a high fat diet
— id: 7363, year: 1999, vol: 80, page: 693, stat: Journal Article,

Comparison of active and cancer registry-based follow-up for breast cancer in a prospective cohort study
Kato I; Toniolo P; Koenig KL; Kahn A; Schymura M; Zeleniuch-Jacquotte A
1999 Feb 15;149(4):372-378, American journal of epidemiology
The authors compared the relative effectiveness of two distinct follow-up designs in prospective cohort studies--the active approach, based on direct contact with study subjects, and the passive approach, based on record linkages with population-based cancer registries--utilizing available information from the New York University Women's Health Study (WHS) and the New York State Cancer Registry (NYSCR). The analyses were limited to breast cancer cases identified during the period 1985-1992, for which follow-up was considered reasonably complete by both the WHS and the NYSCR. Among 12,947 cohort members who reported a New York State address, 303 pathologically confirmed cases were identified through active follow-up and 284 through record linkage. Sixty-three percent of cancers were identified by both sources, 21% by the WHS only, and 16% by the NYSCR only. The agreement was appreciably better for invasive cancers. The percentage of cases identified only by the NYSCR was increased among subjects whose active follow-up was incomplete, as well as among nonwhites, obese patients, and parous patients. This suggests that relying on either type of follow-up alone may introduce certain biases in evaluating risk factors for breast cancer. Combining both approaches appears to be a better strategy in prospective cohort studies
— id: 7364, year: 1999, vol: 149, page: 372, stat: Journal Article,

Epidemiologic correlates with menstrual cycle length in middle aged women
Kato I; Toniolo P; Koenig KL; Shore RE; Zeleniuch-Jacquotte A; Akhmedkhanov A; Riboli E
1999 Oct;15(9):809-814, European journal of epidemiology
While irregular menstruations have been associated with lower cumulative exposure to the ovarian steroids, shorter regular cycles have been postulated to increase the cumulative exposure. Epidemiological correlates with menstrual patterns were analyzed among 4900 premenopausal women aged 45 or younger from the New York University Women's Health Study. The length of regular menstrual cycles increased with increasing age at menarche, body mass index and parity, but decreased with age, nonwhite racial background and current smoking. The likelihood of irregular cycles increased with increasing age, body mass index and number of cigarettes smoked per day. With adjustment for age, body mass index and number of cigarettes smoked per day, the risk of irregular cycles was marginally positively associated with total fat intake
— id: 10358, year: 1999, vol: 15, page: 809, stat: Journal Article,

Onset of natural menopause - Response
Kato, I; Toniolo, P; Akhmedkhanov, A; Koenig, KL; Shore, R; Zeleniuch-Jacquotte, A
1999 DEC ;52(12):1291-1292, Journal of clinical epidemiology
— id: 53844, year: 1999, vol: 52, page: 1291, stat: Journal Article,

Body fat distribution and obesity in pre- and postmenopausal breast cancer
Sonnenschein E; Toniolo P; Terry MB; Bruning PF; Kato I; Koenig KL; Shore RE
1999 Dec;28(6):1026-1031, International journal of epidemiology
BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight
— id: 10351, year: 1999, vol: 28, page: 1026, stat: Journal Article,

Serum autoantibodies recognizing 5-hydroxymethyl-2'-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women
Frenkel K; Karkoszka J; Glassman T; Dubin N; Toniolo P; Taioli E; Mooney LA; Kato I
1998 Jan;7(1):49-57, Cancer epidemiology biomarkers & prevention
Human sera contain anti-5-hydroxymethyl-2'-deoxyuridine (HMdU; an oxidized thymidine) autoantibodies (aAbs), which are significantly higher in chronic inflammatory diseases. The intent of this study was to establish whether anti-HMdU aAbs can serve as predictors of breast and colorectal cancer risk. Sera of 169 women were analyzed by ELISA. Women healthy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMdU aAbs over the age-matched controls (P = 0.028 and P < 0.001, respectively). Subjects diagnosed with rectal cancer had the highest levels of anti-HMdU aAbs (44.80 +/- 11.50; n = 6) in comparison to colon (29.03 +/- 2.49; n = 33) and breast (35.86 +/- 8.55; n = 9) cancers. Individuals with benign breast disease also had elevated anti-HMdU aAb (35.12 +/- 8.77; n = 10), with a borderline statistical significance (P = 0.095), whereas those with benign gastrointestinal tract diseases had those titers (30.95 +/- 3.64; n = 8) significantly increased (P < 0.02). Anti-HMdU aAb levels in subjects with a family history of any cancer (23.57 +/- 2.86; n = 55) did not significantly differ from those of the controls (19.41 +/- 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral disease) showed increased levels (34.48 +/- 8.16; n = 8; P = 0.024). Ps for linear trend of age-adjusted odds ratios were 0.049 for breast and < 0.001 for colorectal cancers. Anti-HMdU aAb titers showed a remarkable stability over a period of 6 years, with a low (14%) intraindividual variance. Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise healthy women who had a family history of breast cancer; in those who had benign breast disease or benign gastrointestinal tract diseases; and, most importantly, in those who at 0.5-6 years after the initial blood donation developed breast or colorectal cancer
— id: 8027, year: 1998, vol: 7, page: 49, stat: Journal Article,

Accuracy of self-report of breast implants
Garbers S; Terry MB; Toniolo P
1998 Mar;101(3):695-698, Plastic & reconstructive surgery
The accuracy of self-report of breast implants was analyzed using a random sample of 130 of 850 available records from a retrospective cohort study of women who underwent cosmetic surgical procedures from 1963 to 1985. Women with breast implants correctly reported having the surgery 89.3 percent of the time, whereas women having other cosmetic surgical procedures correctly reported having the index surgery 92.7 percent of the time. Younger age at surgery, younger age at survey response, and higher level of education were significantly associated with higher sensitivity of self-report. Despite high validity of reporting of surgery, accuracy of self-report of time of surgery was low, with only 9 percent of women who reported their breast implant surgery providing the correct month and year of surgery. These results are in contrast with a previous validity study
— id: 7573, year: 1998, vol: 101, page: 695, stat: Journal Article,

Prospective study of factors influencing the onset of natural menopause
Kato I; Toniolo P; Akhmedkhanov A; Koenig KL; Shore R; Zeleniuch-Jacquotte A
1998 Dec;51(12):1271-1276, Journal of clinical epidemiology
Late or early menopause has been implicated in risk of several chronic diseases in women. To study factors influencing the onset of natural menopause, the authors analyzed the follow-up data of 4694 premenopausal women who enrolled in the New York University Women Study at ages 34-61. In an average of 5.4 years of observation, there were 2035 incidences of menopause, with the median age of 51.3 years. Current smokers experienced menopause 0.75 years earlier than never-smokers. Those who smoked more than 10 cigarettes per day had a 40% increase in risk of earlier menopause. In contrast, women who had three or more children experienced menopause 0.86 years later than nulliparous women, and Jewish women, 0.66 years later than Catholic women. There was also a modest increase in the age at menopause with increasing body mass index. This prospective study provides solid epidemiologic evidence that several factors other than cigarette smoking have impact on the onset of natural menopause
— id: 6062, year: 1998, vol: 51, page: 1271, stat: Journal Article,

Effect of supplementation with chromium picolinate on antibody titers to 5-hydroxymethyl uracil
Kato I; Vogelman JH; Dilman V; Karkoszka J; Frenkel K; Durr NP; Orentreich N; Toniolo P
1998 Sep;14(6):621-626, European journal of epidemiology
Recent in vitro studies have shown that chromium (III) compounds such as chromium picolinate, a popular dietary supplement among people trying to lose weight, produce chromosome damage. We monitored levels of DNA damage in a chromium picolinate supplement trial by measuring antibodies titers to an oxidized DNA base, 5-hydroxymethyl-2'-deoxyuridine (HMdU), by enzyme-linked immunosorbent assays. Ten obese volunteer women completed a 8-week course of 400 micrograms chromium picolinate per day. In either absolute titers or percent of the baseline value, there were no changes in antibody titers at 4 or 8 weeks. The titers were very stable within individuals and those of one individual rarely crossed over others, which was reflected in an intraclass correlation coefficient of 0.99 (95% confidence interval: 0.96-1.00). There were no effects on glucose and lipid metabolism in this period. The results of this trial suggest that chromium (III) picolinate in a dose typically used for nutrient supplementation dose not increase oxidative DNA damage, as measured by anti-HMdU antibody levels
— id: 7626, year: 1998, vol: 14, page: 621, stat: Journal Article,

Molecular markers of exposure to cadmium and nickel among alkaline battery workers
Taioli, E; Frenkel, K; Tagesson, C; Baranski, B; Ganguly, S; Karkoszka, J; Toniolo, P; Cohen, B; Garte, S
1998 MAR-APR ;3(2):129-140, Biomarkers
The goal of the study was to evaluate the usefulness of metallothionein mRNA, anti-5-hydroxymethyl-2'-deoxyuridine antibodies titres (anti-HMdU Ab), and 8-hydroxydeoxyguanosine (8OHdG) in urine as markers of the biologically active dose after exposure to airborne cadmium and nickel in human studies. Exposed persons (n = 38) were chosen from workers involved in the production and assembly, chemistry, and maintenance departments of a nickel-cadmium battery factory in Poland. Controls (n = 52) were chosen from administration personnel at the factory. Biological samples from workers were collected twice: once in the summer, after a month of vacation, and again in the winter, after 3 months of regular working activity within the plant. Controls were recruited during the second phase of the study. When exposure groups were defined on the basis of ambient air cadmium measurements, we found a two-fold increase in mean metallothionein mRNA values in the highest exposure group (air cadmium above 1000 mu g m(-3)) and a positive correlation of metallothionein mRNA with blood cadmium levels (r = 0.46, p < 0.008). Future studies can be designed to investigate further the inter- and intra-subject component of the variability and the possibility of the existence of MT gene polymorphisms, determining different responses and susceptibilities to cadmium exposure. We did not find any difference in the mean values of anti-HMdU Ab titres and 8OHdG in urine in any of the exposure groups analysed. Nickel exposure appeared to have greater impact on anti-HMdU Ab titres than cadmium
— id: 53516, year: 1998, vol: 3, page: 129, stat: Journal Article,

Reliability of serum measurements of lignans and isoflavonoid phytoestrogens over a two-year period
Zeleniuch-Jacquotte A; Adlercreutz H; Akhmedkhanov A; Toniolo P
1998 Oct;7(10):885-889, Cancer epidemiology biomarkers & prevention
We examined the distribution and long-term reliability of serum measurements of the two main human lignans, enterolactone and enterodiol, and the isoflavonoid phytoestrogens daidzein, genistein, equol, and O-Desmethylangolensin in the New York University Women's Health Study, a prospective cohort study of sex hormones and breast cancer. Serum samples collected at three yearly visits in 30 premenopausal and 30 postmenopausal women who had not been diagnosed with cancer or cardiovascular disease were included in the study. Assays were carried out by ion-exchange chromatography and capillary gas chromatography-mass spectrometry. Levels of isoflavonoid phytoestrogens were low, often at or below the sensitivity level of the assay. The reliability coefficients for these compounds were also low (< or =0.30). The median levels of enterodiol and enterolactone were 1.52 nmol/liter and 20.2 nmol/liter, respectively, and were comparable with the levels observed in omnivorous Finnish women living in the Helsinki area. A substantial number of women, though, had fairly high levels: for instance, 15% of the assays showed levels of enterolactone greater than the mean level observed in vegetarian Finnish women, i.e., 89.1 nmol/liter (H. Adlercreutz et al., Cancer Detec. Prev., 18: 259-271, 1994). The reliability coefficient of a single measurement of enterolactone was moderately high (0.55), suggesting that serum measurements of this compound could be a useful tool in prospective epidemiological studies with access to repeated blood or serum specimens. For instance, the reliability coefficient of the average of three measurements of enterolactone would be 0.79, a level considered acceptable in light of the other sources of error that are present in epidemiological studies (W. Willett, Stat. Med., 8: 1031-1040, 1989)
— id: 7470, year: 1998, vol: 7, page: 885, stat: Journal Article,

Applying management strategies in molecular epidemiology field studies
Garbers S; Lukanova A; Garte SJ; Toniolo P; Taioli E
1997 Jan-Mar;12(1):63-69, International journal of health planning & management
In conducting field studies of human exposure, we have encountered significant methodological challenges. The management strategy our group developed to conduct two recent studies of environmental health utilizes a collaborative study design process and innovative protocol management tools, and emphasizes community outreach. We present here the phases of planning, development and realization of two studies--one conducted in an environmentally contaminated area, and another in an occupational setting. We show how the use of this management strategy increases the efficiency of field operations and improves variability assessment
— id: 12030, year: 1997, vol: 12, page: 63, stat: Journal Article,

Prospective study of diet and female colorectal cancer: the New York University Women's Health Study
Kato I; Akhmedkhanov A; Koenig K; Toniolo PG; Shore RE; Riboli E
1997 ;28(3):276-281, Nutrition & cancer
The relation between diet and female colorectal cancer was analyzed in a prospective study of 14,727 women aged 34-65 years, who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991. They were followed through the end of 1994 (average 7.1 yrs) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries, resulting in 100 incident cases of colorectal cancer. There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories, total or subclasses of fat, carbohydrate, or dietary fiber, whereas there was an inverse association with total protein. Among major food groups, there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish (relative risk for 4th vs. 1st quartile = 0.49, 95% confidence interval = 0.27-0.89). A similar inverse association was also observed for consumption of dairy products, and this association was explained mainly by calcium, not by other nutrients, such as fat or protein. The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer, whereas the relations with red meat or total fat remained unclear
— id: 10362, year: 1997, vol: 28, page: 276, stat: Journal Article,

Sex hormone-binding globulin in estrogen-dependent cancer and estrogen replacement therapy
Levitz M; Banerjee S; Raju U; Toniolo PG; Shore RE; Nachtigall LE
1997 Sep 26;828:358-365, Annals of the New York Academy of Sciences
— id: 12252, year: 1997, vol: 828, page: 358, stat: Journal Article,

Reproducibility of a food frequency questionnaire used in the New York University Women's Health Study: effect of self-selection by study subjects
Riboli E; Toniolo P; Kaaks R; Shore RE; Casagrande C; Pasternack BS
1997 Jul;51(7):437-442, European journal of clinical nutrition
OBJECTIVE: The aim of the study was to investigate the reproducibility of a food frequency questionnaire (FFQ) used in a cohort of 14,290 women enrolled in the NYU Women's Health Study. DESIGN: A subset of 474 cohort subjects who completed the dietary questionnaire at baseline (FFQ-1) were approached again on the occasion of a second visit to the mammography study centre and asked to complete the questionnaire a second time (FFQ-2) two to four years after FFQ-1. Two to three months later the questionnaire was mailed to the subjects, and they were asked to complete it a third time (FFQ-3). SETTING: A breast cancer screening clinic. SUBJECTS: Of the 474 subjects selected, 100% completed the second questionnaire while only 56% completed and mailed back FFQ-3. This made it possible to compare the long-term reproducibility of dietary intake measurements and baseline dietary habits between the two groups of subjects 'respondents', who agreed to complete the questionnaire a third time, and 'non-respondents', who did not. RESULTS: Among respondents (56% of study subjects), energy-adjusted correlation coefficients for short-term reproducibility between FFQ-2 and FFQ-3 ranged from 0.50-0.64 for nutrients, and from 0.44-0.67 for foods. The long-term reproducibility was lower, ranging from 0.36-0.53 for nutrients, and from 0.31-0.48 for specific food groups. Among those who did not respond to FFQ-3, crude correlations for long-term reproducibility, unadjusted for energy intake, were generally lower than among respondents. Nevertheless, after adjustment for energy intake, correlations for long-term reproducibility (FFQ-2 to FFQ-1) were of similar magnitude in both groups. In addition, 'non-respondents' reported lower intake of fruit and vegetables and higher intake of meat. CONCLUSIONS: The results of this study suggest that subjects who volunteer to participate in substudies on the validity or reproducibility of dietary questionnaire measurements may tend to provide more accurate responses to the questionnaire. The phenomenon seems related more to accuracy of reporting of absolute intake levels than of the relative composition of diet, self-selection may be associated with differences in dietary habits
— id: 10263, year: 1997, vol: 51, page: 437, stat: Journal Article,

Blood levels of DDT and breast cancer risk among women living in the north of Vietnam
Schecter A; Toniolo P; Dai LC; Thuy LT; Wolff MS
1997 Nov;33(4):453-456, Archives of environmental contamination & toxicology
A positive association has been reported between elevated tissue organochlorines (p,p'-DDT/p,p'-DDE, PCBs, dioxins) and breast cancer in some case-control studies and occupational cohort studies. We previously reported high serum levels of p,p'-DDT and its metabolite p,p'-DDE in women living throughout Vietnam. We report here the results of a small hospital-based case-control study examining the association between blood levels of p,p'-DDT/p,p'-DDE and the risk of invasive breast cancer among residents of the north of Vietnam-an area where insecticides such as p,p'-DDT have been heavily used in the recent past. The study was conducted among patients admitted to a single hospital in the capital city of Hanoi in 1994. Study subjects were 21 women newly diagnosed with invasive adenocarcinoma of the breast, who served as cases, and 21 women of similar age with fibrocystic breast disease, who served as controls. No increase was evident in the relative risk of breast cancer with increasing tertiles of serum concentration of the compounds of interest, even after adjustment for major potential confounders, such as age at menarche, parity, history of lactation, and body weight. These results suggest that recent and past exposure to p,p'-DDT does not play an important role in the etiology of breast cancer among women living in a country with a tropical climate where insecticide use for mosquito control is common
— id: 57248, year: 1997, vol: 33, page: 453, stat: Journal Article,

Endogenous estrogens and breast cancer risk: the case for prospective cohort studies
Toniolo PG
1997 Apr;105 Suppl 3:587-592, Environmental health perspectives
It is generally agreed that estrogens, and possibly androgens, are important in the etiology of breast cancer, but no consensus exists as to the precise estrogenic or androgenic environment that characterizes risk, or the exogenous factors that influence the hormonal milieu. Nearly all the epidemiological studies conducted in the 1970s and 1980s were hospital-based case-control studies in which specimen sampling was performed well after the clinical appearance of the disease. Early prospective cohort studies also had limitations in their small sample sizes or short follow-up periods. However, more recent case-control studies nested within large cohorts, such as the New York University Women's Health Study and the Ormoni e Dieta nell'Eziologia dei Tumori study in Italy, are generating new data indicating that increased levels of estrone, estradiol and bioavailable estradiol, as well as their androgenic precursors, may be associated with a 4- to 6-fold increase in the risk of postmenopausal breast cancer. Further new evidence, which complements and expands the observations from the latter studies, shows that women with the thickest bone density, which may be a surrogate for cumulated exposure to hormones, experience severalfold increased risk of subsequent breast cancer as compared to women with thin bones. These data suggests that endogenous sex hormones are a key factor in the etiology of postmenopausal breast cancer. New prospective cohort studies should be conducted to examine the role of endogenous sex hormones in blood and urine samples obtained early in the natural history of breast cancer jointly with an assessment of bone density and of other important risk factors, such as mammographic density, physical activity, body weight, and markers of individual susceptibility, which may confer increased risk through an effect on the metabolism of endogenous hormones or through specific metabolic responses to Western lifestyle and diet
— id: 7273, year: 1997, vol: 105 Suppl 3, page: 587, stat: Journal Article,

Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women
Zeleniuch-Jacquotte A; Bruning PF; Bonfrer JM; Koenig KL; Shore RE; Kim MY; Pasternack BS; Toniolo P
1997 Jun 1;145(11):1030-1038, American journal of epidemiology
The authors examined the relation between postmenopausal serum levels of testosterone and dehydroepiandrosterone sulfate (DHEAS) and subsequent risk of breast cancer in a case-control study nested within the New York University Women's Health Study cohort. A specific objective of their analysis was to examine whether androgens had an effect on breast cancer risk independent of their effect on the biologic availability of estrogen. A total of 130 cases of breast cancer were diagnosed prior to 1991 in a cohort of 7,054 postmenopausal women who had donated blood and completed questionnaires at a breast cancer screening clinic in New York City between 1985 and 1991. For each case, two controls were selected, matching the case on age at blood donation and length of storage of serum specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees C since sampling. The present report includes a subset of 85 matched sets, for whom at least 6 months had elapsed between blood donation and diagnosis of the case. In univariate analysis, testosterone was positively associated with breast cancer risk (odds ratio (OR) for the highest quartile = 2.7, 95% confidence interval (CI) 1.1-6.8, p < 0.05, test for trend). However, after including % estradiol bound to sex hormone-binding globulin (SHBG) and total estradiol in the statistical model, the odds ratios associated with higher levels of testosterone were considerably reduced, and there was no longer a significant trend (OR for the highest quartile = 1.2, 95% CI 0.4-3.5). Conversely, breast cancer risk remained positively associated with total estradiol levels (OR for the highest quartile = 2.9, 95% CI 1.0-8.3) and negatively associated with % estradiol bound to SHBG (OR for the highest quartile = 0.05, 95% CI 0.01-0.19) after adjustment for serum testosterone levels. These results are consistent with the hypothesis that testosterone has an indirect effect on breast cancer risk, via its influence on the amount of bioavailable estrogen. No evidence was found of an association between DHEAS and risk of breast cancer in postmenopausal women
— id: 7290, year: 1997, vol: 145, page: 1030, stat: Journal Article,

Monitoring human lymphocytic DNA-protein cross-links as biomarkers of biologically active doses of chromate
Costa M; Zhitkovich A; Toniolo P; Taioli E; Popov T; Lukanova A
1996 Oct;104 Suppl 5:917-919, Environmental health perspectives
A simple and sensitive assay for DNA-protein cross-links has been used as a biomarker of chromate exposure and early carcinogenic effects. Pilot studies of DNA-protein cross-links in peripheral blood lymphocytes have been conducted with individuals who had higher exposure to chromate, including welders, and with individuals who had lower levels of exposure such as residents living in a chromium-contaminated area in Jersey City, New Jersey. Studies were also conducted in two Bulgarian cities (Jambol and Burgas) with different levels of air pollution and Cr(VI) exposure and in chrome platers in Bulgaria who had high exposure to chromate. DNA-protein cross-links in U.S. welders and in individuals living in Hudson County, New Jersey around chromium-contaminated areas were significantly higher compared to matched controls. Although blood and urinary levels of chromium were not extensively studied in these populations, we were able to obtain these measurements in the Bulgarian population. Chromium levels in red blood cells of controls living in Burgas were in the order of 1 to 2 ppb chromium, and these individuals had the lowest levels of DNA-protein cross-links. However, the chromium levels in Jambol ranged from about 2 to 7 ppb in red blood cells of city residents to about 22 ppb in chrome platers. DNA-protein cross-links were saturated at about 7 to 8 ppb chromium in the red blood cells, and cross-links correlated well only with chromium levels in red blood cells. Urinary chromium levels did not correlate well with either DNA-protein cross-links or chromium levels in with red blood cells
— id: 12521, year: 1996, vol: 104 Suppl 5, page: 917, stat: Journal Article,

Human metallothionein gene expression determined by quantitative reverse transcription-polymerase chain reaction as a biomarker of cadmium exposure
Ganguly S; Taioli E; Baranski B; Cohen B; Toniolo P; Garte SJ
1996 Apr;5(4):297-301, Cancer epidemiology biomarkers & prevention
Expression of the metallothionein (MT) gene in frozen human lymphocytes has been developed as a new molecular biomarker of heavy metal exposure. Workers at a Polish battery factory with high exposure to cadmium were monitored for airborne exposure and blood cadmium levels. A novel quantitative reverse transcription-PCR (RT-PCR) technique, making use of a homologous internal standard, was used to assess the level of MT-specific mRNA in frozen stored aliquots of blood samples taken from exposed and control workers. Results from this assay showed a statistically significant 2.5-fold increase in MT mRNA in exposed compared to control workers. The RT-PCR results also showed significant correlation with airborne cadmium, as registered on personal monitors and with blood cadmium levels. The results suggest that gene induction measured by quantitative RT-PCR is a promising approach for application as a biomarker of biologically effective dose in small samples of frozen tissues or cells
— id: 10373, year: 1996, vol: 5, page: 297, stat: Journal Article,

Distribution of composite CYP1A1 genotypes in Africans, African-Americans and Caucasians
Garte SJ; Trachman J; Crofts F; Toniolo P; Buxbaum J; Bayo S; Taioli E
1996 May-Jun;46(3):121-127, Human heredity
We present the genotype distribution of the CYP1A1 gene in a sample of over 300 subjects of various ethnic origins. Genotypes are presented as composites of eight possible alleles, taking into account the three major polymorphisms, including a recently described African-American-specific MspI RFLP. A new nomenclature system is presented for clarifying the various haplotypes. Interesting interracial differences in allelic frequencies and admixture rates were observed for the three polymorphisms. Because of the importance of the CYP1A1 gene (which encodes the aromatic hydrocarbon hydroxylase) as a biomarker of genetic susceptibility to environmental carcinogens such as polycyclic aromatic hydrocarbons, these data may provide a useful reference for future studies of relationships between CYP1A1 genotype and disease susceptibility
— id: 56814, year: 1996, vol: 46, page: 121, stat: Journal Article,

Occupational exposure to Cr(VI): comparison between chromium levels in lymphocytes, erythrocytes, and urine
Lukanova A; Toniolo P; Zhitkovich A; Nikolova V; Panev T; Popov T; Taioli E; Costa M
1996 ;69(1):39-44, International archives of occupational & environmental health
The relationships between chromium (Cr) levels in lymphocytes, erythrocytes, urine, and ambient air were compared among 14 chrome-platers from a metallurgic plant in Bulgaria and two groups of local controls, one from the same heavily polluted industrial town as the chrome-platers (n = 11) and one from a seaside resort town 100 km away (n = 6). Among the chrome-platers, the Cr concentration in peripheral lymphocytes was positively correlated with total Cr and Cr(VI) levels in ambient air and with Cr excretion in urine. As compared to the controls, the chrome-platers had mean Cr levels in lymphocytes twice as high, in erythrocytes ninefold higher, and in urine fourfold to eightfold higher. Although Cr levels in urine and lymphocytes were similar between the two control groups, levels in erythrocytes were 3 times higher among subjects from the industrial area than among those from the seaside town. The study suggests that lymphocyte Cr could be a good indicator of the Cr body burden caused by high exposures to Cr(VI), such as in electroplating operations. In these conditions, erythrocyte Cr may be less useful, possibly owing to increased toxicity due to the high affinity of erythrocytes for Cr. However, when exposure is lower, such as in most environmental situations, erythrocyte Cr should provide a better and more sensitive index than lymphocyte Cr. By contrast, urinary Cr, which provides information on total Cr exposure, including Cr(III) from dietary and environmental sources, does not seem to be of value for studying occupational exposure to Cr(VI)
— id: 10374, year: 1996, vol: 69, page: 39, stat: Journal Article,

Temperature variations in upright mechanical freezers
Su SC; Garbers S; Rieper TD; Toniolo P
1996 Feb;5(2):139-140, Cancer epidemiology biomarkers & prevention
We examined temperature deviations from the set temperature in specific locations, between-freezer temperature variability, and the effect of defrosting on temperature deviation in a group of 15 upright mechanical freezers, part of a biological sample bank of a large prospective cohort study. By using an Omega Type T Thermocouple Microcomputer thermometer with the freezers set at -80 degrees C, the internal temperature (12 locations in each freezer) ranged from -90 degrees C to -43.5 degrees C. Overall, internal temperatures tended to be appreciably warmer in the upper and front sections of the freezers. Upright front-loading mechanical freezers, which are widely used in research laboratories throughout the world, may not be optimally suited to preserve human biological samples for long-term banking in epidemiology
— id: 12651, year: 1996, vol: 5, page: 139, stat: Journal Article,

DNA-protein crosslinks as a biomarker of cis-platinum activity in cancer patients
Taioli, E; Zhitkovich, A; Toniolo, P; Bernstein, J; Blum, R; Costa, M
1996 MAY-JUN ;3(3):439-441, Oncology reports
We have developed a new method to assess the amount of DNA-protein crosslinks (DNA-PC) in peripheral lymphocytes, based on the selective precipitation of the DNA crosslinked to proteins. We assessed the amount of DNA-PC in peripheral lymphocytes of 18 cancer patients who underwent chemotherapy with cis-platinum for the first time. Since the chemotherapy was administered over a two-day period, blood samples were drawn at baseline (before starting the therapy), 4 h after the infusion of the first dose of cis-platinum, the next day (24 h after the first dose, and immediately before the infusion of the second dose), and 2 days later (48 h after the first dose). The mean change of DNA-PC 4 h after therapy was 0.8+/-0.8% (p=0.006), 0.5+/-0.6% after 1 day (p=0.007), and 0.1+/-0.5% after two days (ns). The correlation between DNA-PC changes and cumulative dose of cis-platinum was -0.22 at 4 h, -0.19 after 1 day, and -0.68 at 2 days (p=0.005). The crosslinking effect of cis-platinum seems to vary among individuals and with dose; the DNA-PC may be used to define sub-populations of patients with various degree of sensitivity to the pharmacologic action of this chemotherapeutic agent, and thus to adjust the dosage on an individual basis
— id: 52979, year: 1996, vol: 3, page: 439, stat: Journal Article,

Estimating the prevalence of women with breast implants - Response
Terry, MB; Skovron, ML; Garbers, S; Sonnenschein, E; Toniolo, P
1996 JUN ;86(6):892-892, American journal of public health. AJPH
— id: 52882, year: 1996, vol: 86, page: 892, stat: Journal Article,

Jewish religion and risk of breast cancer
Toniolo PG; Kato I
1996 Sep 14;348(9029):760-760, Lancet
— id: 57370, year: 1996, vol: 348, page: 760, stat: Journal Article,

DNA-protein crosslinks in peripheral lymphocytes of individuals exposed to hexavalent chromium compounds
Zhitkovich, A; Lukanova, A; Popov, T; Taioli, E; Cohen, H; Costa, M; Toniolo, P
1996 APR-JUN ;1(2):86-93, Biomarkers
DNA-protein crosslinks were measured in peripheral blood lymphocytes of chrome-platers and controls from Bulgaria in order to evaluate a genotoxic effect of human exposure to carcinogenic Cr(VI) compounds, Chrome-platers and most of the unexposed controls were from the industrial city of Jambol; some additional controls were recruited from the seaside town of Burgas, The chrome-platers had significantly elevated levels of chromium in pre- and post-shift urine, erythrocytes and lymphocytes compared with the control subjects, The largest differences between the two groups were found in erythrocyte chromium concentrations which are considered to be indicative of Cr(VI) exposure, Despite the significant differences in internal chromium doses, levels of DNA-protein crosslinks were not significantly different between the combined controls and exposed workers, Individual DNA-protein crosslinks, however, correlated strongly with chromium in erythrocytes at low and moderate doses but at high exposures, such as among the majority of chrome-platers, these DMA adducts were saturated at maximum levels, The saturation of DNA-protein crosslinks seems to occur at 7-8 pg I-1 chromium in erythrocytes whereas a mean erythrocyte chromium among the chrome platers was as high as 22.8 mu g I-1. Occupationally unexposed subjects exhibited a significant variability with respect to the erythrocyte chromium concentration, however erythrocyte chromium levels correlated closely with DNA-protein crosslinks in lymphocytes, The controls from Jambol had higher chromium concentrations in erythrocytes and elevated levels of DNA-protein crosslinks compared with Burgas controls, Occupational exposure to formaldehyde among furniture factory workers did not change levels of DNA-protein crosslinks in peripheral lymphocytes. DNA-protein crosslink measurements showed a low intraindividual variability and their levels among both controls and exposed indivduals were not affected by smoking, age or weight
— id: 52703, year: 1996, vol: 1, page: 86, stat: Journal Article,

Epidemiologic follow-up studies of breast augmentation patients
Brinton LA; Toniolo P; Pasternack BS
1995 Apr;48(4):557-563, Journal of clinical epidemiology
Although hundreds of thousands of women in this country have had augmentation mammaplasty, little is known about long-term effects. Clinical studies have documented a decreased ability to detect breast lesions in women with implants, leading to concerns regarding breast cancer risk. There is also anecdotal evidence that implants might have effects on a variety of immune conditions. More recently, concern over carcinogenic effects has heightened given findings that the polyurethane foam, used in a minority of implants to envelope silicone gel, contains chemicals linked to cancer in laboratory animals. Only a few epidemiologic studies on long-term effects have been published, and all have had methodologic limitations, including the possibility of inappropriate comparison rates, limited and/or incomplete follow-up, absence of information on patients characteristics, and lack of specific information on types of implanted material. Several case-control and cohort studies are currently underway which are attempting to overcome methodologic limitations of previous studies. Past descriptive and analytic studies are reviewed. In addition, ongoing follow-up efforts are discussed, with attention given to the methodologic adjuncts necessary for allowing valid assessments of long-term disease effects
— id: 10266, year: 1995, vol: 48, page: 557, stat: Journal Article,

A nested case-control study of mammographic patterns, breast volume, and breast cancer (New York City, NY, United States)
Kato I; Beinart C; Bleich A; Su S; Kim M; Toniolo PG
1995 Sep;6(5):431-438, Cancer causes & control. ccc
The relations of Wolfe mammographic patterns, quantitative mammographic densities, and mammographically estimated breast size to breast cancer risk were investigated prospectively in a case-control study nested in the New York University Women's Health Study, a cohort of 14,291 women in New York City, NY (United States). The archived mammograms of 197 breast cancer cases who were identified during the first 5.5 years of the study and of 521 individually matched controls from the same cohort were retrieved and classified according to Wolfe parenchymal patterns and mammographic densities by two expert radiologists. Breast size and volume were estimated on the mammogram's cranio-caudal projection. In both premenopausal and postmenopausal subjects, the risk of breast cancer increased progressively with increasing density and percent density area. A significantly increased risk was found also for Wolfe pattern DY in premenopausal women and P2 pattern in postmenopausal subjects. In premenopausal women, mammographically determined breast volume and breast height also were associated positively with breast cancer risk. Although the results of the present study confirmed that mammographic parenchymal patterns and densities were important predictors of breast cancer risk, their practical use in screening seems limited due to the high prevalence of high risk patterns
— id: 56829, year: 1995, vol: 6, page: 431, stat: Journal Article,

Estimating the reliability of an exposure variable in the presence of confounders
Kim MY; Pasternack BS; Carroll RJ; Koenig KL; Toniolo PG
1995 Jul 15;14(13):1437-1446, Statistics in medicine
In this paper we discuss estimation of the reliability of an exposure variable in the presence of confounders measured without error. We give an explicit formula that shows how the exposure becomes less reliable as the degree of correlation between the exposure and confounders increases. We also discuss biases in the corresponding logistic regression estimates and methods for correction. Data from a matched case-control study of hormone levels and risk of breast cancer are used to illustrate the methods
— id: 6921, year: 1995, vol: 14, page: 1437, stat: Journal Article,

A PROSPECTIVE-STUDY OF ENDOGENOUS ESTROGENS AND BREAST-CANCER IN POSTMENOPAUSAL WOMEN - REPLY
LEVITZ, M; BANERJEE, S; KOENIG, K; SHORE, RE; TONIOLO, P; ZELENIUCHJACQUOTTE, A
1995 SEP 20 ;87(18):1414-1415, Journal of the National Cancer Institute
— id: 86758, year: 1995, vol: 87, page: 1414, stat: Journal Article,

RE - PREMENOPAUSAL ESTRADIOL LEVELS AND THE RISK OF BREAST-CANCER - A NEW METHOD OF CONTROLLING FOR DAY OF THE MENSTRUAL-CYCLE - REPLY
PASTERNACK, BS; SHORE, RE; KOENIG, KL; TONIOLO, PG; ROSENBERG, CR
1995 APR 15 ;141(8):789-790, American journal of epidemiology
— id: 87373, year: 1995, vol: 141, page: 789, stat: Journal Article,

Radical differences in CYP1A1 genotype and function
Taioli E; Crofts F; Trachman J; Bayo S; Toniolo P; Garte SJ
1995 May;77(1-3):357-362, Toxicology letters
The cytochrome P450 1A1 (CYP1A1) gene may be of critical importance in determining individual cancer susceptibility to aromatic hydrocarbons such as those in tobacco smoke. We compared the frequencies of CYP1A1 haplotypes, and complete genotypes, taking into account polymorphisms at 3 sites, including an African-specific polymorphism. No concordance was observed in Africans or African-Americans between any of the 3 polymorphisms, (Msp1 restriction fragment length polymorphism (RFLP)--'M', exon 7--'E', new RFLP--'A') in contrast to the concordance seen between the M and E polymorphisms in Caucasians and Asians. We observed an effect of the E polymorphism on enzyme activity and mRNA induction in Asians and Caucasians
— id: 10378, year: 1995, vol: 77, page: 357, stat: Journal Article,

A specific African-American CYP1A1 polymorphism is associated with adenocarcinoma of the lung
Taioli E; Crofts F; Trachman J; Demopoulos R; Toniolo P; Garte SJ
1995 Feb 1;55(3):472-473, Cancer research
A case-control study on lung cancer in African-Americans has been conducted to assess whether a novel African-American-specific polymorphism in the CYP1A1 gene increases the susceptibility to tobacco-related lung cancer. The prevalence of the AA RFLP was 17.1% in the DNA extracted from archived tissue blocks from 76 incident cases of lung cancer, and was 16.3% in peripheral blood lymphocyte DNA of 123 healthy African-American volunteers recruited from a community in the eastern United States. The analysis by histological type showed an association between adenocarcinoma (AC) of the lung and the AA RFLP (odds ratio, 2.6; 95% confidence interval, 1.1-6.3). One homozygous variant subject was present among the AC cases. The risk of AC in subjects who both smoke and carry the AA RFLP was more than double, in comparison to subjects who only smoke (relative interaction magnitude under the additive model, 24%). The mean value of pack-year in AC with the polymorphism was 5.0 +/- 2.5 and in AC without the polymorphism was 37.2 +/- 6.5 (P < 0.05). Our data suggest that a selective association exists between the AA polymorphism and adenocarcinoma of the lung and that a lower dose of tobacco is sufficient to exert carcinogenic effects on the adenomatous tissue of subjects carrying the AA polymorphism
— id: 56718, year: 1995, vol: 55, page: 472, stat: Journal Article,

A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women
Taioli E; Trachman J; Chen X; Toniolo P; Garte SJ
1995 Sep 1;55(17):3757-3758, Cancer research
We examined the role of CYP1A1 polymorphisms as potential molecular markers of breast cancer susceptibility in Caucasian and African-American women. The case-control study involved 51 women with breast cancer and 269 female controls. In African-Americans, the frequency of the homozygous MspI polymorphism was 3.5% in controls and 19% in breast cancer cases. The odds ratio of breast cancer with the MspI homozygous variant was 9.7 (95% confidence interval: 2.0-47.9). This association was not observed in Caucasian women. The exon 7 and AA polymorphisms were not associated with breast cancer in either group. The mechanism for the observed association between the MspI polymorphism and breast cancer is unclear. It is possible that the CYP1A1 MspI RFLP is linked with other polymorphisms in the African-American population, either in the CYP1A1 gene, which is involved in estrogen metabolism, or other genes related to risk of breast cancer
— id: 56792, year: 1995, vol: 55, page: 3757, stat: Journal Article,

Increased DNA-protein crosslinks in lymphocytes of residents living in chromium-contaminated areas
Taioli E; Zhitkovich A; Kinney P; Udasin I; Toniolo P; Costa M
1995 Dec;50(3):175-180, Biological trace element research
It has been known for a number of years that chromium-containing mine slags were used as landfill in residential areas of Hudson County, New Jersey. Since one of the major lesions induced in intact cells by chromate is the DNA-Protein crosslink, we have used this lesion as a biomarker of biological effect of chromium (Cr) exposure. We have previously developed a sensitive and easy-to-perform assay to detect DNA-Protein crosslinks, based on the selective K SDS precipitation of DNA associated with protein. We examined the levels of DNA-Protein crosslinks in peripheral blood mononuclear cells of 33 individuals determined to be at risk for chromium exposure by virtue of their residence in Hudson County and their urinary Cr levels. These data were compared to the levels of DNA-Protein crosslinks among 49 controls who resided in noncontaminated areas. A complete clinical examination and urine analysis did not show any Cr-related abnormalities among the exposed population. The mean DNA-Protein crosslink level in the lymphocytes of the exposed group was 1.3 +/- 0.5% (SD), whereas the unexposed group had 0.8 +/- 0.4% (p < 0.001), after adjustment for age, gender, race, smoking, and weight. Further studies in this population are needed to confirm the possible association between the high levels of DNA-Protein crosslink and Cr exposure
— id: 10377, year: 1995, vol: 50, page: 175, stat: Journal Article,

NORMAL VALUES OF DNA-PROTEIN CROSS-LINKS IN MONONUCLEAR BLOOD-CELLS OF A POPULATION OF HEALTHY CONTROLS
TAIOLI, E; ZHITKOVICH, A; TONIOLO, P; COSTA, M
1995 MAR-APR ;8(2):76-79, CANCER JOURNAL
Background - We have previously used a sensitive and simple assay to detect DNA-protein crosslinks, based upon the selective potassium SDS precipitation of DNA associated with protein, DNA-protein crosslinks are a promising biomarker of environmental exposure to carcinogens such as chromate. Methods - We have examined the levels of DNA-protein crosslinks in peripheral blood mononuclear cells of 68 healthy subjects, to determine the normal values of this biomarker in the general population, and to analyze the effect of possible confounding factors, such as age, gender, ethnicity, smoking habits, weight. Results - The mean value of DNA-protein crosslinks was 0.78 +/- 0.04%, No statistically significant differences in DNA-protein crosslinks were observed with gender, ethnicity or weight, No statistically significant correlations were found with age and humber of cigarettes smoked per day. Conclusions - These results set a reference value for DNA-protein crosslinks in healthy subjects,
— id: 87362, year: 1995, vol: 8, page: 76, stat: Journal Article,

The estimated frequency of cosmetic breast augmentation among US women, 1963 through 1988
Terry MB; Skovron ML; Garbers S; Sonnenschein E; Toniolo P
1995 Aug;85(8 Pt 1):1122-1124, American journal of public health. AJPH
Estimates ranging from 1 to 2 million have been used to describe the number of women in the United States who have had cosmetic breast implants. Original data from a historical cohort study of women with breast augmentation were combined with simulation techniques to compute new estimates grounded on a more objective set of information and assumptions than previous attempts. It was estimated that the number of women who had cosmetic augmentation mammoplasty between 1963 and 1988 was 894,206 (range = 437,602 to 2,035,783). The number of women ever treated with cosmetic augmentation mammoplasty may be substantially smaller than previously reported
— id: 56794, year: 1995, vol: 85, page: 1122, stat: Journal Article,

Development of biomarkers of human exposure to carcinogens: the example of DNA-protein cross-links
Toniolo P; Taioli E
1995 May;77(1-3):231-234, Toxicology letters
Biomarkers are considered to be more biologically informative than traditional methods and less prone to misclassification bias. However, new biomarkers are conceived in experimental laboratories and normally undergo extensive experimental in vitro and in vivo testing, usually without regard as to their potential use in humans. Whereas the epidemiologist had no role in the original development of the basic research idea leading to the initial formulation of a biomarker, the new biomarker or technical modification of an existing one are the product of observations in humans. The results of our field studies on DNA-protein cross-links (DPX) among chromate workers illustrates inherent difficulties in the process of development and validation of biomarkers
— id: 56795, year: 1995, vol: 77, page: 231, stat: Journal Article,

A prospective study of endogenous estrogens and breast cancer in postmenopausal women
Toniolo PG; Levitz M; Zeleniuch-Jacquotte A; Banerjee S; Koenig KL; Shore RE; Strax P; Pasternack BS
1995 Feb 1;87(3):190-197, Journal of the National Cancer Institute
BACKGROUND: Circumstantial evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue. PURPOSE: Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease. METHODS: The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14,291 New York City women, 35-65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5 1/2 years of study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35,509 person-years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at -80 degrees C since sampling. RESULTS: For increasing quartiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend = .06); the ORs for increasing quartiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend = .06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4, 3.0, and 2.9 (P value for trend < .01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend < .01), thus suggesting a strong protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn 2 or more years before breast cancer diagnosis. CONCLUSIONS: These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer. IMPLICATIONS: Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman's risk of developing breast cancer later in life
— id: 57459, year: 1995, vol: 87, page: 190, stat: Journal Article,

LIMITATIONS OF NUTRITIONAL DATA - REPLY
TONIOLO, PG; SHORE, RE
1995 JAN ;6(1):90-91, Epidemiology
— id: 87473, year: 1995, vol: 6, page: 90, stat: Journal Article,

Environmental organochlorine exposure as a potential etiologic factor in breast cancer
Wolff MS; Toniolo PG
1995 Oct;103 Suppl 7:141-145, Environmental health perspectives
Known risk factors for breast cancer do not account for a significant proportion of the overall incidence. Reproductive factors and endogenous hormones are thought to be responsible for a large component of risk. An environmental contribution has been sought in the past to explain the international trends in breast cancer rates and changes in risk among migrating populations. Recently, environmental research has turned to investigation of exogenous chemical exposures, including environmental contamination, as potential risk factors that may arise from the hormonal activity or from the carcinogenicity of many of these chemicals. Several reports since 1991 suggest that organochlorines may be a risk factor for breast cancer. The data are strongest for DDT. For PCBs, the results to date have been equivocal if not entirely negative. However, different groups of polychlorinated biphenyl (PCB) congeners are known to provoke biological responses that are structure specific. A wide divergence of estrogenic response, cytochrome P450 activity, and biological half-life exists within these groups of PCB congeners. Therefore, understanding breast cancer risk from PCB exposure requires attention to congener structures in complex mixtures and to temporal changes in exposure. Investigation of environmental contributions to breast cancer risk offers the potential for understanding more about the etiology of this complex disease and may also provide opportunities for prevention of the most common cancer among women in the United States
— id: 8329, year: 1995, vol: 103 Suppl 7, page: 141, stat: Journal Article,

Endogenous estrogens and risk of breast cancer by estrogen receptor status: a prospective study in postmenopausal women
Zeleniuch-Jacquotte A; Toniolo P; Levitz M; Shore RE; Koenig KL; Banerjee S; Strax P; Pasternack BS
1995 Dec;4(8):857-860, Cancer epidemiology biomarkers & prevention
A positive association between postmenopausal serum levels of total estradiol, percentage of free estradiol, and percentage of estradiol not bound to sex hormone-binding globulin (SHBG) and breast cancer risk was recently reported by the New York University Women's Health Study (P. Toniolo et al., J. Natl. Cancer Inst., 87: 190-197, 1995). Data from this prospective study are used to assess whether the observed associations differ according to estrogen receptor (ER) status of the tumor. Between 1985 and 1991, 7063 postmenopausal women donated blood and completed questionnaires at a large breast cancer screening clinic in New York City. Before 1991, 130 cases of first primary breast cancer were identified by active follow-up of the cohort. For each case, two controls were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees since sampling. ER information was abstracted from pathology reports. Separate statistical analyses were conducted of ER-positive, ER-negative, and ER-unknown groups (53, 23, and 54 matched sets, respectively). In each of the 3 groups, the mean estradiol and the mean percentage of free estradiol were greater (21-28% and 6-7%, respectively) in cases than in controls. Conversely, the mean percentage of estradiol bound to SHBG was 9-12% lower in cases than in controls. The logistic regression coefficients measuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the ER-positive, ER-negative, and ER-unknown groups. These data suggest that in postmenopausal women, the association of endogenous estrogens with breast cancer risk is independent of the ER status of the tumor. This result is more compatible with the hypothesis of a progression from ER-positive to ER negative tumors than with the hypothesis that ER status identifies two distinct types of breast cancer
— id: 56859, year: 1995, vol: 4, page: 857, stat: Journal Article,

ENDOGENOUS ESTROGENS AND RISK OF BOAST CANCER BY ESTROGEN-RECEPTOR STATUS
ZELENIUCHJACQUOTTE, A; TONIOLO, P; LEVITZ, M; SHORE, R; KOENIG, K; BANERJEE, S; STRAX, P; PASTERNACK, B
1995 JUN 1 ;141(11):S15-S15, American journal of epidemiology
— id: 87280, year: 1995, vol: 141, page: S15, stat: Journal Article,

Functional significance of different human CYP1A1 genotypes
Crofts F; Taioli E; Trachman J; Cosma GN; Currie D; Toniolo P; Garte SJ
1994 Dec;15(12):2961-2963, Carcinogenesis
At least two different polymorphisms in the human CYP1A1 gene have been associated with an increased risk for tobacco-related lung cancer; however, the functional significance of these polymorphisms has not been determined. We measured CYP1A1 genotypes, gene expression levels and enzymatic activity levels in mitogen-stimulated lymphocytes to determine whether genetic polymorphisms in CYP1A1 alter transcriptional and/or post-transcriptional regulation of the gene. Genotypes were determined at two sites previously associated with lung cancer: a point mutation in exon 7 near the catalytic region of the enzyme and an Msp1 RFLP in the 3' non-coding region of the gene. Variant genotypes at the Msp1 site had no effect on CYP1A1 gene induction, however, variant genotypes at the exon 7 site were significantly associated with increased CYP1A1 gene inducibility. We also observed a significant interaction between the exon 7 polymorphism and smoking on mRNA levels. There was a 3-fold elevation in CYP1A1 enzymatic activity in exon 7 variant genotypes. When Msp1 and exon 7 genotypes were combined, there was an increased CYP1A1 inducibility and enzymatic activity in subjects with the exon 7 polymorphism, and in subjects with both polymorphisms
— id: 6599, year: 1994, vol: 15, page: 2961, stat: Journal Article,

Occupational exposures to Cd, Ni, and Cr modulate titers of antioxidized DNA base autoantibodies
Frenkel K; Karkoszka J; Cohen B; Baranski B; Jakubowski M; Cosma G; Taioli E; Toniolo P
1994 Sep;102 Suppl 3:221-225, Environmental health perspectives
This study was undertaken to establish whether occupational exposures to derivatives of carcinogenic metals evoke inflammatory immune responses, as determined by the presence of elevated titers of antibodies (Ab) that recognize oxidized DNA bases. Sera obtained from the blood of steel welders (Delaware) and from workers of the Centra Ni-Cd Battery Factory (Poznan, Poland) were analyzed by the enzyme-linked immunosorbent assay. To determine specific and nonspecific binding, an oxidized thymidine [5-hydroxymethyl-2'-deoxyuridine (HMdU)] coupled to bovine serum albumin (HMdU-BSA) as well as mock-coupled BSA (M-BSA) were used as antigens for coating the wells of microtiter plates. Titers of anti-HMdU Ab were significantly elevated in the high Cd and Ni exposure groups (18.3 +/- 3.2 vs 10.8 +/- 2.1 A492/microliters; p < 0.05). The sera of the groups with low exposures to Cd and Ni also had enhanced titers of those Ab but those increases were not statistically significant. Interestingly, the Ab titers present in the sera of controls for Cd and Ni exposures appear to be constant regardless of the protein content. In contrast, both lightly and heavily exposed subjects exhibited Ab titers that increased with increasing protein content. When 12 randomly selected workers (4 from each of the control, lightly, and heavily exposed groups) were outfitted with personal monitors, anti-HMdU Ab titers of those workers showed a significant difference between the groups with light (< 100 micrograms/m3) and heavy (> 200 micrograms/m3) exposures to Cd (9.8 +/- 3.7 vs 22.1 +/- 3.7 A492/microliters; p < 0.01) and Ni (11.7 +/- 1.4 vs 31.0 +/- 1.8; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 6621, year: 1994, vol: 102 Suppl 3, page: 221, stat: Journal Article,

Premenopausal estradiol levels and the risk of breast cancer: a new method of controlling for day of the menstrual cycle [see comments]
Rosenberg CR; Pasternack BS; Shore RE; Koenig KL; Toniolo PG
1994 Sep 15;140(6):518-525, American journal of epidemiology
Levels of total estradiol in premenopausal women vary widely over the course of the menstrual cycle with a spike at the time of ovulation and dissimilar patterns pre- and post-ovulation. Evaluating the association between breast cancer and premenopausal measurements of total estradiol when the measurements cannot be taken on a uniform day of the cycle is therefore a difficult methodological challenge. In a matched case-control study of breast cancer nested within a prospective study, premenopausal serum samples obtained up to 7 years before breast cancer diagnosis were available for total estradiol assay. By fitting a three-piece spline model that regressed the logarithm of total estradiol (ln estradiol) on day of menstrual cycle, the authors were able to adjust the measurements for day of the cycle on which they were collected by expressing them in terms of the number of standard deviations above or below the fitted ln estradiol value for that day. Applying the adjusted measurements to the nested case-control study, they found evidence of a 1.5 to 2-fold risk for women in the upper two tertiles of ln estradiol relative to women in the lowest tertile. Conditional logistic regression analysis for day-of-cycle-adjusted ln estradiol treated as a continuous variable resulted in a relative risk estimate of 1.19 (95% confidence interval 0.91-1.55) per standard-deviation increase in adjusted ln estradiol
— id: 10268, year: 1994, vol: 140, page: 518, stat: Journal Article,

Application of reliability models to studies of biomarker validation
Taioli E; Kinney P; Zhitkovich A; Fulton H; Voitkun V; Cosma G; Frenkel K; Toniolo P; Garte S; Costa M
1994 Mar;102(3):306-309, Environmental health perspectives
We present a model of biomarker validation developed in our laboratory, the results of the validation study, and the impact of the estimation of the variance components on the design of future molecular epidemiologic studies. Four different biomarkers of exposure are illustrated: DNA-protein cross-link (DNA-PC), DNA-amino acid cross link (DNA-AA), metallothionein gene expression (MT), and autoantibodies to oxidized DNA bases (DNAox). The general scheme for the validation experiments involves n subjects measured on k occasions, with j replicate samples analyzed on each occasion. Multiple subjects, occasions, and replicates provide information on intersubject, intrasubject, and analytical measurement variability, respectively. The analysis of variance showed a significant effect of batch variability for DNA-PC and MT gene expression, whereas DNAox showed a significant between-subject variability. Among the amino acids tested, cysteine and methionine showed a significant contribution of both batch and between-subject variability, threonine showed between-subject variability only, and tyrosine showed between-batch and between-subject variability. The total variance estimated through the experiment was used to calculate the minimum sample size required for a future epidemiologic study including the same biomarkers used for the reliability study. Such validation studies can detect the various components of variability of a biomarker and indicate needed improvements of the assay, along with possible use in field studies
— id: 10381, year: 1994, vol: 102, page: 306, stat: Journal Article,

Reliability of measurements of total, protein-bound, and unbound estradiol in serum
Toniolo P; Koenig KL; Pasternack BS; Banerjee S; Rosenberg C; Shore RE; Strax P; Levitz M
1994 Jan-Feb;3(1):47-50, Cancer epidemiology biomarkers & prevention
Estradiol (E2) circulates in the blood in three states: unbound (U-E2), bound to sex-hormone binding globulin (SHBG-E2), and bound to albumin. There is evidence to support the concept that only U-E2 and albumin-bound E2, are bioavailable (i.e., rapidly extracted by tissues). A case-control study nested within a large cohort of women, in which we are examining the effect of estrogens on breast cancer risk, offered the opportunity to assess the reliability of measurements of E2, the percentage of SHBG-E2, and the percentage of U-E2 based on multiple annual serum specimens. Long-term (1-2 year) reliability, as estimated by the intraclass correlation coefficient, was assessed in a subgroup of 71 premenopausal and 77 postmenopausal controls for whom two or three serum specimens were assayed. In postmenopausal women the intraclass correlation coefficient for a single measurement of total E2 was only 0.51. As for the percentage of SHBG-E2, intraclass correlation coefficients were 0.83 and 0.94, and for U-E2, 0.72 and 0.77 in the premenopausal and postmenopausal groups, respectively. These data suggest that, whereas single determinations of total E2 are insufficient to reliably estimate a woman's true mean level, a single measurement of the percentage of SHBG-E2 or U-E2 is adequate to assess bioavailability of E2 in an epidemiological study, irrespective of day of the menstrual cycle
— id: 56598, year: 1994, vol: 3, page: 47, stat: Journal Article,

Consumption of meat, animal products, protein, and fat and risk of breast cancer: a prospective cohort study in New York
Toniolo P; Riboli E; Shore RE; Pasternack BS
1994 Jul;5(4):391-397, Epidemiology
Epidemiologic studies have focused on the association between diet and breast cancer with conflicting results. Whereas a majority of case-control studies indicate a role for the intake of total fat and saturated fat, most prospective cohort studies either are negative or indicate very modest associations. Only a few authors have examined the role of meat intake in relation to breast cancer risk. The aim of this study was to examine the relation between risk of breast cancer and dietary intake of meat, animal products, fat, and protein. Between 1985 and 1991, we recruited 14,291 New York City women in a prospective cohort study of endogenous hormones, diet, and cancer in which they reported on their recent diet using a food frequency questionnaire self-administered at enrollment. From the cohort, 180 invasive breast cancer cases diagnosed before December 1990 and five times as many controls, individually matched by age, calendar time at enrollment, menopausal status, and, if premenopausal, phase of menstrual cycle, were included in a nested case-control study. There was an evident increase in the relative risk (RR) of breast cancer for increasing consumption of meat. Women in the upper quintile of meat consumption, as compared with the lowest quintile, had an energy-adjusted RR of 1.87 (95% confidence interval = 1.09-3.21). There was a modest RR increase in the upper quintile of total and saturated fat and no apparent association for other types of fat, protein, dairy products, poultry, or fish.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 56722, year: 1994, vol: 5, page: 391, stat: Journal Article,

DDT AND BREAST-CANCER - RESPONSE
WOLFF, MS; TONIOLO, PG
1994 JUL 20 ;86(14):1095-1096, Journal of the National Cancer Institute
— id: 52417, year: 1994, vol: 86, page: 1095, stat: Journal Article,

Racial differences in restriction fragment length polymorphisms and messenger RNA inducibility of the human CYP1A1 gene
Cosma G; Crofts F; Currie D; Wirgin I; Toniolo P; Garte SJ
1993 Jan-Feb;2(1):53-57, Cancer epidemiology biomarkers & prevention
Recent studies have examined the relationship between genetic polymorphisms of the human cytochrome P-4501A1 (CYP1A1) gene and lung cancer susceptibility. We have quantified genotypic frequencies and measured gene expression in the CYP1A1 gene within racially diverse groups in order to determine the relationship between genotype and transcriptional regulation of the CYP1A1 gene. Lymphocytes were obtained from 68 individuals of European-American, African-American, and Asian descent, and CYP1A1 gene inducibility was measured in mitogen-stimulated cells. CYP1A1 gene inducibility was significantly lower in African-Americans than in European-Americans or Asians, while several other population parameters were found to have no effect on gene expression levels. Restriction fragment length polymorphism analysis of lymphocyte DNA following MspI restriction enzyme digestion revealed a significant difference in the frequencies of CYP1A1 genotypes between European-Americans and Asians. The only homozygous variants detected were of Asian descent. The frequencies of CYP1A1 genotypes in all races conformed to Hardy-Weinberg genotypic equilibrium. When CYP1A1 gene inducibility was compared to CYP1A1 genotype, no significant correlations were found. These studies, along with our previous survey of CYP1A1 gene expression in creosote-exposed workers, add further support to the use of CYP1A1 gene inducibility as a potential marker of polycyclic aromatic hydrocarbon exposure in human populations
— id: 10391, year: 1993, vol: 2, page: 53, stat: Journal Article,

Relationship between genotype and function of the human CYP1A1 gene
Cosma G; Crofts F; Taioli E; Toniolo P; Garte S
1993 Oct-Nov;40(2-3):309-316, Journal of toxicology & environmental health
A comparative study of human CYP1A1 genotypes and enzymatic activity was performed in a racially diverse population in order to determine frequencies of CYP1A1 genetic polymorphisms and the relationship between CYP1A1 genotype and function. Restriction fragment length polymorphism analyses revealed significantly higher frequencies of a variant Msp1 polymorphism in Asians versus European-Americans, while African-American CYP1A1 genotypic frequencies more closely approximated those of Asians. Comparison of CYP1A1 genotypes at the Msp1 locus to a polymorphic site in exon 7 of the gene revealed a higher frequency of variant genotypes at the Msp1 site. Measurement of lymphocyte CYP1A1 enzyme activity by the ethoxyresorufin O-deethylase assay revealed significantly elevated levels of inducible enzyme activity among variant exon 7 genotypes when compared to wild-type genotypic individuals. These results demonstrate racially distinct patterns of CYP1A1 genotypes, and suggest a functional link between genotype and catalytic activity of the cytochrome P-450 protein responsible for the metabolism of many carcinogenic polycyclic aromatic hydrocarbons
— id: 56516, year: 1993, vol: 40, page: 309, stat: Journal Article,

Preliminary report on a simple new assay for DNA-protein cross-links as a biomarker of exposures experienced by welders
Costa M; Zhitkovich A; Taioli E; Toniolo P
1993 Oct-Nov;40(2-3):217-222, Journal of toxicology & environmental health
A method originally developed to detect topoisomerase DNA complexes has been adapted to determine DNA-protein cross-links formed in cells following their exposure in vitro and in vivo to cross-linking agents. A preliminary study on welders and controls has been carried out to assess the feasibility of this assay to detect human exposure to chromium (Cr) and nickel (Ni) that are associated with increased DNA-protein cross-links. The percentage of cross-link was significantly higher among welders (1.85% +/- 1.14) than among controls (1.17% +/- 0.46; p = .01) Cross-links were not affected by age, weight, or smoking status. The assay developed has substantial advantages over previous methods, being considerably more simple, inexpensive, and sensitive
— id: 6343, year: 1993, vol: 40, page: 217, stat: Journal Article,

DNA-protein cross-links in welders: molecular implications
Costa M; Zhitkovich A; Toniolo P
1993 Feb 1;53(3):460-463, Cancer research
A new method for detecting DNA-protein cross-links involving selective precipitation of DNA containing cross-linked proteins by K(+)-sodium dodecyl sulfate was utilized in the peripheral WBC of 21 male metal arc welders and in 26 male controls of similar age and racial characteristics who were not exposed to welding fumes. DNA was quantitated by Hoechst fluorescence. Although the concentration of nickel and chromium in the peripheral blood did not differ between subjects in the two groups, one-fourth of the welders had levels of DNA-protein cross-links that were above the upper limit of the controls. Mean cross-link values were 1.85 +/- 1.14% (SD) among the welders and 1.17 +/- 0.46% among the controls, a 58% statistically significant difference (P = 0.01). Thus, many welders appeared to be burdened with an excess of DNA-protein cross-links, suggesting exposure to cross-linking agents and, possibly, a detectable biological effect of potential genotoxic consequences
— id: 10386, year: 1993, vol: 53, page: 460, stat: Journal Article,

A novel CYP1A1 gene polymorphism in African-Americans [published erratum appears in Carcinogenesis 1993 Dec;14(12):2652]
Crofts F; Cosma GN; Currie D; Taioli E; Toniolo P; Garte SJ
1993 Sep;14(9):1729-1731, Carcinogenesis
A new Msp1 RFLP in the CYP1A1 gene has been found in genomic DNA from African-Americans. The polymorphism results from a single A-T to G-C transition in the 3' noncoding region approximately 300 bp upstream from the polyadenylation site. This mutation leads to cleavage of the normal 2.3 kb MspI restriction fragment into 1.3 and 1.0 kb fragments. The heterozygous mutation has been seen in 8 of 47 African-Americans, but was not detected in 191 Caucasians or 30 Asians. No linkage was observed with either of the two previously described polymorphisms in this gene
— id: 6345, year: 1993, vol: 14, page: 1729, stat: Journal Article,

BLOOD-LEVELS OF ORGANOCHLORINE RESIDUES AND RISK OF BREAST-CANCER - RESPONSE
DUBIN, N; TONIOLO, PG; LEE, EW; WOLFF, MS
1993 OCT 20 ;85(20):1696-1697, Journal of the National Cancer Institute
— id: 52200, year: 1993, vol: 85, page: 1696, stat: Journal Article,

Reliability of serum prolactin measurements in women
Koenig KL; Toniolo P; Bruning PF; Bonfrer JM; Shore RE; Pasternack BS
1993 Sep-Oct;2(5):411-414, Cancer epidemiology biomarkers & prevention
Prolactin, a hormone indispensable for milk secretion, has been shown to enhance the development and growth of mammary tumors in rodents; however, its importance in human breast cancer is uncertain. Serum prolactin levels are known to fluctuate considerably under normal conditions, and lack of precision in the hormone measurements may have contributed to the largely negative findings in humans to date. The purpose of this study was to investigate the reliability of prolactin measurements in women using stored serum from an ongoing prospective study of breast cancer. Separate groups of postmenopausal and premenopausal women who donated multiple blood samples at approximately 1-year intervals were studied. The reliability of a single log prolactin determination, as measured by the intraclass correlation coefficient, was 0.76 for the postmenopausal women (95% confidence interval, 0.66-0.85) and 0.48 for the premenopausal women (95% confidence interval, 0.31-0.62). These findings suggest that a single measurement is sufficient to characterize the serum prolactin level of postmenopausal women for epidemiological research. For premenopausal women, however, multiple samples are desirable. Controlling for phase of the menstrual cycle does not appear to substantially improve the reliability of premenopausal measurements
— id: 6424, year: 1993, vol: 2, page: 411, stat: Journal Article,

PROSPECTIVE-STUDY OF SERUM PROLACTIN AND BREAST-CANCER
KOENIG, K; TONIOLO, P; BRUNING, P; BONFRER, J; SHORE, R; ZELENIUCHJACQUOTTE, A; PASTERNACK, B
1993 OCT 15 ;138(8):601-601, American journal of epidemiology
— id: 52160, year: 1993, vol: 138, page: 601, stat: Journal Article,

Sources of variability in waist and hip measurements in middle-aged women
Sonnenschein EG; Kim MY; Pasternack BS; Toniolo PG
1993 Sep 1;138(5):301-309, American journal of epidemiology
The reliability of single measurements of waist and hip circumference and the ratio of waist circumference to hip circumference (a widely used measure of body fat distribution) has not been fully examined. The authors analyzed measurements of waist and hip circumference, as well as self-reported weight and height, repeated 3-6 times between 1986 and 1991 among 1,851 participants in the New York University Women's Health Study. Quetelet index (weight (kg)/height (m)2) was positively correlated with waist circumference (r = 0.88), hip circumference (r = 0.89), and waist/hip ratio (r = 0.52). Mean weight was positively correlated with the within-subject variance of waist circumference (r = 0.27) and, to a lesser degree, with the within-subject variance of hip circumference (r = 0.08) and waist/hip ratio (r = 0.10). The within-subject variance of weight was positively correlated with the within-subject variance of waist (r = 0.30) and hip (r = 0.23) measurements, and less so with waist/hip ratio (r = 0.05). Intraclass correlations for waist, hip, and waist/hip ratio were 0.89, 0.81, and 0.74, respectively; adjustment for Quetelet index reduced the intraclass correlations for waist and hip measures by 33% and 48%, respectively. Such adjustment can provide a more realistic determination of the reliability associated with an exposure variable in the design and analysis of studies investigating the relation between body fat distribution and disease
— id: 8308, year: 1993, vol: 138, page: 301, stat: Journal Article,

Development and utilization of a new simple assay for DNA-protein crosslinks as a biomarker of exposure to welding fumes
Toniolo P; Zhitkovich A; Costa M
1993 ;65(1 Suppl):S87-S89, International archives of occupational & environmental health
A new method for DNA-protein crosslinks involving selective precipitation of DNA containing crosslinked proteins by K+ sodium dodecyl sulfate was utilized in the peripheral white blood cells of 21 male metal arc welders and in 26 male controls of similar age and racial characteristics who were not exposed to welding fumes. DNA was quantitated by Hoescht fluorescence. Although the concentration of nickel and chromium in the peripheral blood was low and did not differ between subjects in the two groups, one-fourth of the welders had levels of DNA-protein crosslinks that were above the upper limit of the controls. Mean crosslink values were 1.85% (+/- 1.14) among the welders and 1.17% (+/- 0.46) among the controls, a 58%, statistically significant difference (P = 0.01). Thus, many welders appeared to be burdened with an excess of DNA-protein crosslinks suggesting exposure to crosslinking agents and, possibly, a detectable biologic effect of potential genotoxic consequences
— id: 6540, year: 1993, vol: 65, page: S87, stat: Journal Article,

PROSPECTIVE-STUDY OF ENDOGENOUS ESTROGENS AND BREAST-CANCER
TONIOLO, P; LEVITZ, M; JACQUOTTE, A; KOENIG, K; SHORE, R; PASTERNACK, B
1993 OCT 15 ;138(8):601-601, American journal of epidemiology
— id: 52159, year: 1993, vol: 138, page: 601, stat: Journal Article,

Blood levels of organochlorine residues and risk of breast cancer
Wolff, M S; Toniolo, P G; Lee, E W; Rivera, M; Dubin, N
1993 Apr 21;85(8):648-652, Journal of the National Cancer Institute
BACKGROUND: Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases. PURPOSE: This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women. METHODS: We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer. RESULTS: Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE. CONCLUSION: In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs. IMPLICATIONS: These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far-reaching for public health intervention worldwide
— id: 138933, year: 1993, vol: 85, page: 648, stat: Journal Article,

ORGANOCHLORINES AND BREAST-CANCER - RESPONSE
WOLFF, MS; DUBIN, N; TONIOLO, PG
1993 NOV 17 ;85(22):1873-1875, Journal of the National Cancer Institute
— id: 52163, year: 1993, vol: 85, page: 1873, stat: Journal Article,

Expression of the CYP1A1 gene in peripheral lymphocytes as a marker of exposure to creosote in railroad workers
Cosma GN; Toniolo P; Currie D; Pasternack BS; Garte SJ
1992 Jan-Feb;1(2):137-142, Cancer epidemiology biomarkers & prevention
We have conducted a pilot study to assess levels of cytochrome CYP1A1 gene expression in human peripheral lymphocytes as a molecular biomarker assay for polycyclic hydrocarbon exposure. Basal and 3-methylcholanthrene-induced levels of gene expression were measured by standard slot-blot mRNA analyses in mitogen-stimulated cultures of peripheral blood lymphocytes from creosote-exposed railroad workers and unexposed control subjects. Dermal and inhalation exposure of workers to creosote may vary substantially as a function of working conditions related to temperature. Therefore, blood specimens were collected from separate groups during the winter, fall, and summer. Basal and induced CYP1A1 gene expression levels were not elevated in workers from any of the three seasonal studies. However, induced/basal (inducibility) CYP1A1 mRNA ratios from workers sampled in the summer (when actual exposures were greatest) were significantly higher when compared to those of controls (P < 0.01). These studies demonstrate the potential usefulness of specific gene expression assays in human peripheral lymphocytes for the assessment of carcinogen exposure in human populations
— id: 10271, year: 1992, vol: 1, page: 137, stat: Journal Article,

Reproducibility of Wolfe's classification of mammographic parenchymal patterns
Toniolo P; Bleich AR; Beinart C; Koenig KL
1992 Jan;21(1):1-7, Preventive medicine
BACKGROUND: Inadequate reproducibility of Wolfe's classification of mammographic parenchymal patterns may explain its limited use in clinical and screening practice. If the misclassification of mammographic parenchymal pattern categories is substantial, inconsistencies in study results will occur, which could at least partially explain the frequent inability to replicate Wolfe's findings in studies of breast cancer. In this article, results of a study to determine whether consensus to resolve inconsistencies between raters would improve the level of concordance in mammographic parenchymal pattern categorization and thus help reduce misclassification are presented. METHODS. One hundred consecutive mammograms from a large screening clinic in New York City were classified independently by two expert mammographers on two separate occasions, 8 days apart. Coding was repeated in two consensus conferences several weeks later. Reliability was estimated by computing intraclass correlation coefficients. RESULTS: Initially, the average intraobserver reliability for the four patterns was 0.68 and the interobserver reliability was 0.65. After consensus, reliability improved markedly to 0.88. CONCLUSION: It is concluded that the added complication and cost of consensus ratings will be more than offset by a substantial increase in precision
— id: 13713, year: 1992, vol: 21, page: 1, stat: Journal Article,

RE - POLYCYSTIC OVARIES AND THE RISK OF BREAST-CANCER
TONIOLO, P; WHITTEMORE, AS
1992 AUG 1 ;136(3):372-373, American journal of epidemiology
— id: 51858, year: 1992, vol: 136, page: 372, stat: Journal Article,

THE ASSOCIATION BETWEEN ALCOHOL AND BREAST-CANCER RISK - EVIDENCE FROM THE COMBINED ANALYSIS OF 6 DIETARY CASE-CONTROL STUDIES
Howe, G; Rohan, T; Decarli, A; Iscovich, J; Kaldor, J; Katsouyanni, K; Marubini, E; Miller, A; Riboli, E; Toniolo, P; Trichopoulos, D
1991 Mar 12;47(5):707-710, International journal of cancer
Data from 1,575 cases and 1,974 controls enrolled in 6 previously conducted case-control studies of diet and breast cancer have been analysed with respect to alcohol intake. There appears to be an absence of any association between consumption of up to 40 g of alcohol per day and risk of breast cancer, and a highly statistically significant and consistent elevated risk of breast cancer for drinkers of 40 g or more of alcohol per day, for whom the relative risk, as compared with that of non-drinkers, is 1.69 (95% confidence interval 1.19 to 2.40). This association is not due to confounding by a number of diet-related factors, including total calories, fat, fibre and vitamin C
— id: 32190, year: 1991, vol: 47, page: 707, stat: Journal Article,

RELIABILITY OF SERUM PROLACTIN MEASUREMENTS
KOENIG, KL; TONIOLO, P; BONFRER, JMG; PASTERNACK, BS; SHORE, RE; BRUNING, PF
1991 OCT 1 ;134(7):753-753, American journal of epidemiology
— id: 51536, year: 1991, vol: 134, page: 753, stat: Journal Article,

SERUM AND URINARY ANDROGENS AND RISK OF BREAST-CANCER IN POSTMENOPAUSAL WOMEN
Secreto, G; Toniolo, P; Berrino, F; Recchione, C; Cavalleri, A; Pisani, P; Totis, A; Fariselli, G; Dipietro, S
1991 May 15;51(10):2572-2576, Cancer research
Serum levels of testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin and urinary levels of testosterone and androstanediol were compared in 75 women with breast carcinoma and 150 age-matched healthy controls. Odds ratios for quartiles of hormones, adjusted for known potential confounders, were computed using conditional logistic regression. Risk of breast cancer was positively associated with levels of all androgens in serum and urine but appeared stronger for testosterone (for trend, P = 0.03) and dehydroepiandrosterone sulfate (for trend, P = 0.06) in serum and for testosterone (for trend, P = 0.001) and androstanediol (for trend, P = 0.04) in urine. The adjusted odd ratios for high versus low quartiles were 2.7 (95% confidence interval, 1.1-6.5) for serum testosterone, 2.8 (1.1-7.4) for dehydroepiandrosterone sulfate, 4.7 (1.8-12.1) for urinary testosterone, and 3.4 (1.4-8.7) for urinary androstanediol. These observations suggest that endogenous androgenic hormones may play an important role in the epidemiology of postmenopausal breast cancer in women
— id: 32182, year: 1991, vol: 51, page: 2572, stat: Journal Article,

A community study of alcohol consumption and dietary habits in middle-aged Italian women
Toniolo P; Riboli E; Cappa AP
1991 Sep;20(3):663-670, International journal of epidemiology
This population-based study examines whether dietary intake in middle-aged Italian women is influenced by alcohol drinking habits. The 499 participants were interviewed using a dietary history questionnaire designed to investigate alcohol consumption. Mean intake of total and non-alcohol energy increased progressively within categories of increasing alcohol consumption (less than 5, 5-19, 20-39, 40+ g/day). Mean body weight and Quetelet index (kg/m2), however, decreased with increasing alcohol consumption. Once the disparities in energy intake were reduced by computing intake densities, the data suggest that moderate and heavy drinkers have dietary habits similar to those of abstainers or light drinkers. These findings were confirmed by multiple linear regression analyses in which the confounding effects of age, place of residence, occupation, and Quetelet index were taken into account. Increasing alcohol consumption appeared associated only with a modest decrease in the intake of fibre, beta-carotene, and vitamin C. These findings do not support the hypothesis that the observed protection from coronary artery disease among moderate drinkers is related to a chronic reduction in the intake of carbohydrates and fat, at least in middle-aged women
— id: 13902, year: 1991, vol: 20, page: 663, stat: Journal Article,

Endogenous hormones and breast cancer: a prospective cohort study [see comments]
Toniolo PG; Pasternack BS; Shore RE; Sonnenschein E; Koenig KL; Rosenberg C; Strax P; Strax S
1991 May;18 Suppl 1:S23-S26, Breast cancer research & treatment
A cohort study is under way in New York City to evaluate how levels of endogenous reproductive hormones influence the risk of breast cancer. The study, in which approximately 15,000 women are being recruited, utilizes a prospective design in which volunteers are asked to provide repeated specimens of serum during the period 1985-1992. A case-control study nested within the cohort is planned by which specimens from all cases arising in the population and from a randomly selected sample of time-matched controls will be analyzed and compared. As of December 31, 1989, 13,609 volunteers had donated blood specimens, about 50% of whom had already donated more than once. Of the 187 incident breast cancer cases who are expected to arise in the cohort before the end of 1992, 77 have been detected thus far
— id: 6539, year: 1991, vol: 18 Suppl 1, page: S23, stat: Journal Article,

RELIABILITY OF PERCENT ESTRADIOL BINDING TO PROTEINS - IMPLICATIONS FOR STUDY DESIGN
TONIOLO, P; PASTERNACK, B; KOENIG, K; ROSENBERG, C; SHORE, R; BANERJEE, S; LEVITZ, M
1991 OCT 1 ;134(7):774-775, American journal of epidemiology
— id: 51537, year: 1991, vol: 134, page: 774, stat: Journal Article,

NONOCCUPATIONAL RISK INDICATORS OF GLIOBLASTOMA IN ADULTS
Hochberg, F; Toniolo, P; Cole, P
1990 Feb;8(1):55-60, Journal of neuro-oncology
— id: 31894, year: 1990, vol: 8, page: 55, stat: Journal Article,

DIETARY FACTORS AND RISK OF BREAST-CANCER - COMBINED ANALYSIS OF 12 CASE CONTROL STUDIES
Howe, GR; Hirohata, T; Hislop, TG; Iscovich, JM; Yuan, JM; Katsouyanni, K; Lubin, F; Marubini, E; Modan, B; Rohan, T; Toniolo, P; Shunzhang, Y
1990 Apr 4;82(7):561-569, Journal of the National Cancer Institute
— id: 31994, year: 1990, vol: 82, page: 561, stat: Journal Article,

[Diet and breast cancer. A population study in the Vercelli Province]
Toniolo P; Riboli E; Cappa AP
1990 Dec;12(45):59-61, Epidemiologia e prevenzione
— id: 14262, year: 1990, vol: 12, page: 59, stat: Journal Article,

DIETARY-FAT INTAKE AND BREAST-CANCER RISK - RESPONSE
Riboli, E; Toniolo, P
1989 Sep 20;81(18):1423-1424, Journal of the National Cancer Institute
— id: 31671, year: 1989, vol: 81, page: 1423, stat: Journal Article,

ANDROGENS AND BREAST-CANCER IN PREMENOPAUSAL WOMEN
Secreto, G; Toniolo, P; Pisani, P; Recchione, C; Cavalleri, A; Fariselli, G; Totis, A; Dipietro, S; Berrino, F
1989 Jan 15;49(2):471-476, Cancer research
— id: 31652, year: 1989, vol: 49, page: 471, stat: Journal Article,

MAMMOGRAPHIC PARENCHYMAL FEATURES AND BREAST-CANCER
Sonnenschein, E; Toniolo, P
1989 Jun 21;81(12):962-963, Journal of the National Cancer Institute
— id: 31690, year: 1989, vol: 81, page: 962, stat: Journal Article,

RISK OF BREAST-CANCER, DIET AND INTERNAL MIGRATIONS IN NORTHERN ITALY
Toniolo, P; Protta, F; Cappa, APM
1989 Oct 31;75(5):406-409, Tumori
— id: 31902, year: 1989, vol: 75, page: 406, stat: Journal Article,

BREAST-CANCER AND ALCOHOL-CONSUM
Toniolo, P; Riboli, E; Protta, F; Cappa, APM
1989 Oct;130(4):811-811, American journal of epidemiology
— id: 31667, year: 1989, vol: 130, page: 811, stat: Journal Article,

BREAST-CANCER AND ALCOHOL-CONSUM
Toniolo, P; Riboli, E; Protta, F; Charrel, M; Cappa, APM
1989 Sep 15;49(18):5203-5206, Cancer research
— id: 31624, year: 1989, vol: 49, page: 5203, stat: Journal Article,

CALORIE-PROVIDING NUTRIENTS AND RISK OF BREAST-CANCER
Toniolo, P; Riboli, E; Protta, F; Charrel, M; Cappa, APM
1989 Feb 15;81(4):278-286, Journal of the National Cancer Institute
— id: 31647, year: 1989, vol: 81, page: 278, stat: Journal Article,

Public health aspects of toxic chemical disposal sites
Upton AC; Kneip T; Toniolo P
1989 ;10:1-25, Annual review of public health
— id: 10793, year: 1989, vol: 10, page: 1, stat: Journal Article,

ANDROGENS AND BREAST-CANCER IN PREMENOPAUSAL WOMEN
Toniolo, P; Secreto, G; Pisani, P; Recchione, C; Cavalleri, A; Berrino, F
1988 Sep;12(1):140-140, Breast cancer research & treatment
— id: 31437, year: 1988, vol: 12, page: 140, stat: Journal Article,

Breast cancer detection centers and case-control studies of the efficacy of screening
Dubin N; Friedman DR; Toniolo PG; Pasternack BS
1987 ;40(11):1041-1050, Journal of chronic diseases
Case-control studies of screening efficacy have been proposed as a cost- and time-efficient alternative to randomized controlled trials. Possible source populations for such retrospective studies of breast cancer screening are considered, including women from (i) pre-existing randomized trials, (ii) non-experimental population-based studies and (iii) detection centers. On practical grounds women attending detection centers are seen to comprise the most readily accessible source of adequate numbers of cases and controls. Potential biases are addressed, involving incomplete case ascertainment, self-selection, and different screening recommendations. Data from the Guttman Breast Diagnostic Institute are used for illustration
— id: 10275, year: 1987, vol: 40, page: 1041, stat: Journal Article,

ESTIMATING INCIDENCE OF CANCER FROM A HOSPITAL DISCHARGE REPORTING SYSTEM
TONIOLO, P; PISANI, P; VIGANO, C; GATTA, G; REPETTO, F
1986 JUL ;34(1):23-30, Revue d'epidemiologie & de sante publique
— id: 41579, year: 1986, vol: 34, page: 23, stat: Journal Article,