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Trabert B.,Hormonal and Reproductive Epidemiology Branch | Wentzensen N.,Hormonal and Reproductive Epidemiology Branch | Yang H.P.,Hormonal and Reproductive Epidemiology Branch | Sherman M.E.,Hormonal and Reproductive Epidemiology Branch | And 4 more authors.
British Journal of Cancer | Year: 2012

Background: Women using unopposed estrogens during menopause are at increased risk of ovarian cancer. It is uncertain whether oestrogen plus progestin therapy exerts similar effects. Methods: We evaluated menopausal hormone use and incident ovarian cancer (n426) in 92 601 post-menopausal women enrolled in the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study. Participants were administered questionnaires in 1996-1997 and followed through 2006. Hazard rate ratios (RR) and 95% confidence intervals (CIs) were estimated using Cox regression. Results: Increased risks were associated with long duration (10 years) use of unopposed oestrogen (RR 2.15, 95% CI: 1.30-3.57 among women with a hysterectomy) and oestrogen plus progestin (RR 1.68, 95% CI: 1.13-2.49 among women with intact uteri) therapy. Similar risks were associated with progestins that were used sequentially (15 days progestin per month) (RR 1.60, 95% CI: 1.10-2.33) or continuously (25 days progestin per month) (RR 1.43, 95% CI: 1.032-2.01; P-value for heterogeneity0.63).Conclusion:Our findings suggest that long duration use of both unopposed estrogens and oestrogen plus progestins are associated with increased risks of ovarian cancer, and that risk associated with oestrogen plus progestin use does not vary by regimen (sequential or continuous). © 2012 Cancer Research UK All rights reserved. Source

Yang H.P.,U.S. National Cancer Institute | Wentzensen N.,U.S. National Cancer Institute | Trabert B.,U.S. National Cancer Institute | Gierach G.L.,U.S. National Cancer Institute | And 6 more authors.
American Journal of Epidemiology | Year: 2013

On the basis of clinical and pathologic criteria, endometrial carcinoma has been distinguished as Types I (mainly endometrioid) and II (nonendometrioid). Limited data suggest that these subtypes have different risk factor profiles. The authors prospectively evaluated risk factors for Types I (n = 1,312) and II (n = 138) incident endometrial carcinoma among 114,409 women in the National Institutes of Health (NIH)-AARP Diet and Health Study (1995-2006). For individual risk factors, relative risks were estimated with Cox regression by subtype, and Pheterogeneity was assessed in case-case comparisons with Type I as the referent. Stronger relations for Type I versus Type II tumors were seen for menopausal hormone therapy use (relative risk (RR) of 1.18 vs. 0.84; Pheterogeneity = 0.01) and body mass index of ≥30 vs. <30 kg/m2 (RR of 2.93 vs. 1.83; Pheterogeneity = 0.001). Stronger relations for Type II versus Type I tumors were observed for being black versus white (RR of 2.18 vs. 0.66; Pheterogeneity = 0.0004) and having a family history of breast cancer (RR of 1.93 vs. 0.80; P heterogeneity = 0.002). Other risk factor associations were similar by subtype. In conclusion, the authors noted different risk factor associations for Types I and II endometrial carcinomas, supporting the etiologic heterogeneity of these tumors. Because of the limited number of Type II cancers, additional evaluation of risk factors will benefit from consortial efforts. © 2012 The Author. Source

Patel K.,Meharry Medical College | Hargreaves M.K.,Meharry Medical College | Liu J.,Meharry Medical College | Schlundt D.,Vanderbilt University | And 7 more authors.
American Journal of Health Behavior | Year: 2011

Objectives: To examine the relationship between smoking and weight status in adult women and whether this association differed by race. Methods: The study sample consisted of 22,949 African American and 7831 white women enrolled in the Southern Community Cohort Study from 2002 to 2006. Results: Both African American and white current smokers had decreased odds of being overweight or obese compared to normal-weight nonsmokers, and the inverse trends between current smoking and BMI held for both groups. Conclusion: A strong relationship exists between smoking and weight status, with patterns nearly identical for African Americans and white women. Copyright (c) PNG Publications. All rights reserved. Source

Mondul A.M.,Nutritional Epidemiology Branch | Yu K.,Biostatistics Branch | Wheeler W.,Management Information Services Inc. | Zhang H.,Fudan University | And 18 more authors.
Human Molecular Genetics | Year: 2011

Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10 -17) and rs10882272 (P =6.04× 10 -12). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10 -5), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10 -5). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases. © The Author 2011. Published by Oxford University Press. All rights reserved. Source

Guertin K.A.,Nutritional Epidemiology Branch | Moore S.C.,Nutritional Epidemiology Branch | Sampson J.N.,Biostatistics Branch | Huang W.-Y.,Occupational and Environmental Epidemiology Branch | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2014

Background: Metabolomics is an emerging field with the potential to advance nutritional epidemiology; however, it has not yet been applied to large cohort studies. Objectives: Our first aim was to identify metabolites that are biomarkers of usual dietary intake. Second, among serum metabolites correlated with diet, we evaluated metabolite reproducibility and required sample sizes to determine the potential for metabolomics in epidemiologic studies. Design: Baseline serum from 502 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was analyzed by using ultra-high- performance liquid-phase chromatography with tandem mass spectrometry and gas chromatography-mass spectrometry. Usual intakes of 36 dietary groups were estimated by using a food-frequency questionnaire. Dietary biomarkers were identified by using partial Pearson's correlations with Bonferroni correction for multiple comparisons. Intraclass correlation coefficients (ICCs) between samples collected 1 y apart in a subset of 30 individuals were calculated to evaluate intraindividual metabolite variability. Results: We detected 412 known metabolites. Citrus, green vegetables, red meat, shellfish, fish, peanuts, rice, butter, coffee, beer, liquor, total alcohol, and multivitamins were each correlated with at least one metabolite (P < 1.093. 10-6; r = -0.312 to 0.398); in total, 39 dietary biomarkers were identified. Some correlations (citrus intake with stachydrine) replicated previous studies; others, such as peanuts and tryptophan betaine, were novel findings. Other strong associations included coffee (with trigonelline-N-methylnicotinate and quinate) and alcohol (with ethyl glucuronide). Intraindividual variability in metabolite levels (1-y ICCs) ranged from 0.27 to 0.89. Large, but attainable, sample sizes are required to detect associations between metabolites and disease in epidemiologic studies, further emphasizing the usefulness of metabolomics in nutritional epidemiology. Conclusions: We identified dietary biomarkers by using metabolomics in an epidemiologic data set. Given the strength of the associations observed, we expect that some of these metabolites will be validated in future studies and later used as biomarkers in large cohorts to study diet-disease associations. The PLCO trial was registered at clinicaltrials.gov as NCT00002540. © 2014 American Society for Nutrition. Source

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