We propose the continued follow-up of a prospective cohort of 116,678 female nurses, aged 25-42 in 1989 (Nurses' Health Study II), to assess specific proposed risk factors for breast cancer, melanoma, and infertility. The five major specific hypotheses we will address are presented as questions to be addressed: 1. Does use of oral contraceptives increase the risk of breast cancer? In particular, does extended use of oral contraceptives before first pregnancy increase this risk? 2. Do higher levels of physical activity, particularly in adolescence and young adulthood, reduce risk of breast cancer? 3. Does alcohol intake in early adulthood increase breast cancer risk, and are higher levels of vitamin A-intake during this period protective? 4. Does use of oral contraceptives increase risk of melanoma? 5. Are extremes of body mass index, smoking, specific dietary factors, increased levels of physical activity, and menstrual characteristics related to risk of infertility? To accomplish this, we will maintain follow-up of the cohort by mailing questionnaires at two-year intervals to update information on exposure status and to ascertain incident cases of non-fatal diagnoses of cancer and other health outcomes, which will be further documented by review of medical records. Follow-up of this cohort to date has been exceptionally high. Deaths among non-respondents will be ascertained by use of the National Death Index. Exposure status for oral contraceptive use and physical activity will be updated by using instruments validated in this cohort. Dietary exposures will be measured using a food frequency questionnaire extensively validated in the original Nurses' Health Study. We will have substantial power to examine the above hypotheses by the end of the fourth cycle of follow-up (in 1998). This study will not only provide essential information for women and their physician making decisions or contraceptive practice, but also serve as a base for examining other etiologies of breast cancer as well as causes of other diseases that affect younger women, such as cardiovascular disease and diabetes.
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