In this competing renewal, we propose to build upon and extend our recent work on endogenous hormones and risk of breast cancer and also to evaluate several new breast cancer hypotheses. In addition, we propose to address a number of new hypotheses in relation to risk of ovarian cancer, a highly lethal cancer in women for which few prospective evaluations of biomarkers have been conducted. To accomplish these aims, we will conduct two nested case-control studies using already collected biologic samples from the Nurses' Health Study (for breast and ovarian cancers), and both the Women's Health Study and Nurses' Health Study II (for ovarian cancer only). Specifically, we will evaluate plasma estrogen metabolites, prolactin (using two blood samples collected 10 years apart), urinary melatonin, and urinary vs. plasma estrone sulfate, all in relation to breast cancer risk. Further, we will evaluate the independent contribution of endogenous sex steroids to the Gall and Rosner individual breast cancer risk prediction models. We also will evaluate plasma insulin like growth factors, androgens, vitamin D, and polymorphisms in both the progesterone receptor and vitamin D receptor in relation to ovarian cancer risk. Our proposed ovarian cancer aims, with 282 cases in plasma analyses and 521 cases in genetic analyses (all with 2 controls per case), will provide either the first or by far the most detailed prospective assessment of these potentially important risk factors. Finally, as a methodologic aim, we propose several pilot studies to evaluate the feasibility of using mass spectrometry technology (SELDI-TOF) in our cohorts to identify plasma protein profiles that predict subsequent cancer risk. Overall, the large size of these cohorts, their prospective design, high follow-up rates, detailed exposure data collected over many years, and the availability of archived plasma, DNA and urine specimens provides a unique opportunity to test a number of hypotheses of public health importance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA049449-19
Application #
7355566
Study Section
Special Emphasis Panel (ZRG1-BMRD (02))
Program Officer
Schully, Sheri D
Project Start
1989-06-01
Project End
2009-06-30
Budget Start
2008-03-01
Budget End
2009-06-30
Support Year
19
Fiscal Year
2008
Total Cost
$1,213,763
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
O'Reilly, Éilis J; Bjornevik, Kjetil; Schwarzschild, Michael A et al. (2018) Pre-diagnostic plasma urate and the risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 19:194-200
Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi et al. (2018) Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies. BMJ 360:j5644
Earp, Madalene; Tyrer, Jonathan P; Winham, Stacey J et al. (2018) Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility. PLoS One 13:e0197561
O'Mara, Tracy A; Glubb, Dylan M; Amant, Frederic et al. (2018) Identification of nine new susceptibility loci for endometrial cancer. Nat Commun 9:3166
Hamada, Tsuyoshi; Khalaf, Natalia; Yuan, Chen et al. (2018) Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer. Clin Gastroenterol Hepatol 16:1300-1306.e3
Song, Mingyang; Zheng, Yan; Qi, Lu et al. (2018) Longitudinal Analysis of Genetic Susceptibility and BMI Throughout Adult Life. Diabetes 67:248-255
Van Dyke, Alison L; Langhamer, Margaret S; Zhu, Bin et al. (2018) Family History of Cancer and Risk of Biliary Tract Cancers: Results from the Biliary Tract Cancers Pooling Project. Cancer Epidemiol Biomarkers Prev 27:348-351
Chen, Steven T; Li, Xin; Han, Jiali (2018) Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women. Int J Cancer 142:1536-1541
Li, Bo; Wang, Yanru; Xu, Yinghui et al. (2018) Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival. Int J Cancer 142:2303-2312
Rist, Pamela M; Jiménez, Monik C; Tworoger, Shelley S et al. (2018) Plasma Retinol-Binding Protein 4 Levels and the Risk of Ischemic Stroke among Women. J Stroke Cerebrovasc Dis 27:68-75

Showing the most recent 10 out of 526 publications