We propose to continue the follow-up of 116,678 women, who were 25 to 42 years of age in 1989 when enrolled in the prospective Nurses' Health Study II, which was designed to identify potentially modifiable determinants of breast cancer risk in young women. In this unique cohort, information on oral contraceptive use, diet, physical activity, and other exposures has been collected at two-year intervals with 90% or greater response to each follow-up questionnaire. Since the initiation of the cohort, we have collected blood (stored as plasma, red cells, and buffy coats for DNA) and urine samples from approximately 30,000 participants and detailed data on current and high school diet. Important findings have emerged on animal fat consumption and use of oral contraceptive preparations containing levonorgestrel. In the present proposals, we will address several hypotheses relating specific nutritional factors during high school and early adult life (assessed as dietary intakes and blood levels), acrylamide intake from dietary sources, use of specific formulations of oral contraceptives, shift work and melatonin excretion, lifetime physical activity, exclusive breast feeding, and plasma cysteine levels to risk of pre- and postmenopausal breast cancer. These analyses will incorporate specific gene-environment interactions and the methylation status of BRCA-1 in tumor blocks. To carry out these aims and expand the core resources, we propose to collect buccal cell samples for DNA from 30,000 participants who did not provide blood. With follow-up though 2007, we anticipate a total of 2773 incident cases of breast cancer, including 1946 in premenopausal women, which will provide adequate power to address these issues. The follow-up of this population will provide women and their health care providers with information critical for informed decisions regarding use of oral contraceptives, diet, and other aspects of lifestyle, and will also contribute to better understanding of the etiology and prevention of breast cancer in young women.
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