We propose to analyze blood samples in a nested case-control manner from the 32,826 participants in the Nurses' Health Study (NHS) who provided samples in 1989-90 and were 43 to 69 years of age at that time. The samples have been stored at greater than or equal to 130 C in liquid nitrogen freezers since collection. We will assay samples from women who were diagnosed after blood collection and matched controls who remained disease-free, thus efficiently utilizing these prospectively collected samples. We propose to build upon our recent positive findings for several plasma hormones and nutrients in relation to breast and colon cancer risk, and to address new hormonal hypotheses in relation to risk of breast, ovarian and colon cancers and myocardial infarction. Specifically, we will examine (1) plasma estrogens, androgens and prolactin levels in relation to breast cancer risk in postmenopausal women, (2) a polymorphism in the catechol-O- methyl transferase (COMT) gene and risk of breast cancer, (3) DHEA, DHEAS and 5-androstene-3beta,17beta-diol and risk of breast and ovarian cancers and myocardial infarction, (4) insulin-like growth factor I and its binding proteins 1 and 3, plasma vitamin D and polymorphisms in the vitamin D receptor, and plasma antioxidant levels - all in relation to risk of breast and colon cancers. The ongoing NHS (CA40356 and HL34594) will provide follow-up and documentation of disease outcomes in addition to providing information on important covariates (such as exogenous hormone use, diet, smoking status, among others) for the proposed study. Participation in the NHS has been high: among the 32,826 women who provided a blood sample, 98 percent continue to complete questionnaires, and vital status has been documented for 99 percent. Overall, the large size of the cohort, the prospective design, the high follow-up rate, the detailed exposure data, and the availability of archived blood specimens provide a unique opportunity to test several hypotheses of public health importance. We also propose to collect a second blood sample from about 18,000 of the women who provided a first blood sample in 1989-90. This will increase our statistical power in future analyses, and allow us to assess in detail the temporal relationships between biomarkers and disease risk and to reduce the attenuating effects of measurement error.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA049449-10
Application #
2751295
Study Section
Special Emphasis Panel (ZRG4-HPD (08))
Program Officer
Patel, Appasaheb1 R
Project Start
1989-06-01
Project End
2004-03-31
Budget Start
1999-09-16
Budget End
2000-03-31
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Lu, Yingchang; Beeghly-Fadiel, Alicia; Wu, Lang et al. (2018) A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk. Cancer Res 78:5419-5430
Chiu, Yu-Han; Bertrand, Kimberly A; Zhang, Shumin et al. (2018) A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non-Hodgkin lymphoma. Int J Cancer 143:1914-1922
Kim, Hanseul; Keum, NaNa; Giovannucci, Edward L et al. (2018) Garlic intake and gastric cancer risk: Results from two large prospective US cohort studies. Int J Cancer 143:1047-1053
Bailey, Jessica N Cooke; Gharahkhani, Puya; Kang, Jae H et al. (2018) Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci 59:629-636
Chang, Shun-Chiao; Crous-Bou, Marta; Prescott, Jennifer et al. (2018) Prospective association of depression and phobic anxiety with changes in telomere lengths over 11 years. Depress Anxiety 35:431-439
Li, Jun; Rice, Megan S; Huang, Tianyi et al. (2018) Circulating prolactin concentrations and risk of type 2 diabetes in US women. Diabetologia 61:2549-2560
Barbhaiya, Medha; Tedeschi, Sara K; Lu, Bing et al. (2018) Cigarette smoking and the risk of systemic lupus erythematosus, overall and by anti-double stranded DNA antibody subtype, in the Nurses' Health Study cohorts. Ann Rheum Dis 77:196-202
Zong, Geng; Valvi, Damaskini; Coull, Brent et al. (2018) Persistent organic pollutants and risk of type 2 diabetes: A prospective investigation among middle-aged women in Nurses' Health Study II. Environ Int 114:334-342

Showing the most recent 10 out of 526 publications