We propose to analyze blood samples in a """"""""nested"""""""" case-control manner from the 32,825 participants in the Nurses' Health Study (NHS) who provided samples in 1989-1990 and were 43 to 69 years of age at that time. The samples have been stored at less than or equal to 130 degrees C, in liquid nitrogen freezers, since collection. Laboratory analyses will be conducted on plasma samples from women who developed disease after donating a blood sample and matched controls who remained disease-free, thus efficiently utilizing these prospectively collected samples. We will concentrate on several major hypotheses, i.e., hormonal and nutritional determinants of disease risk. Specifically, we will examine (1) endogenous hormone levels (estradiol [both free and bound fractions], estrone, androgens, progesterone and prolactin) in relation to breast cancer risk in postmenopausal women, (2) antioxidant levels in relation to risk of breast cancer, (3) levels of folate, iron, fatty acids, antioxidants and vitamin D in relation to both colon cancer and colon polyps, and (4) levels of lipids, fatty acids, homocysteine, folate, ferritin and antioxidants in relation to risk of myocardial infarction and stroke. Most of the nutrients we propose to examine are hypothesized to influence development of both cancer and cardiovascular disease, thus the analyses will provide a better understanding of the influence of these factors on overall disease risk. The ongoing NHS will provide follow-up and documentation of cancers (CA 40356) and cardiovascular outcomes (HL 34594) in addition to information on important covariates (such as exogenous hormone use, other dietary factors, smoking status, and body mass index, among others) for the proposed study. Participation in the NHS has been high: of the 121,700 women, approximately 90% continue to respond to the questionnaires, and vital status has been documented for >98%. 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 a number of hypotheses of public health importance.
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