Mammographic density is currently considered our best surrogate endpoint for breast cancer risk. However, determinants of mammographic density are not well understood. Age, menopausal status, body size, and parity collectively explain less than half of the total variance in mammographic density. The main objective of this grant application is to follow-up on our previous leads on dietary and genetic determinants of mammographic density. We propose to conduct a cost-effective cross-sectional study among 2,200 postmenopausal Chinese women in Singapore who were participants of both the Singapore Chinese Health Study, a prospective cohort study of cancer, and the nationwide mammography screening program. As part of entry into the cohort study, these women were interviewed in person and provided detailed lifestyle information and completed a validated 165-item food frequency questionnaire. Blood specimens (for genotyping) and mammograms are already available on these 2,200 women. We propose to assess mammographic density using a computer-assisted method we developed and have successfully employed in epidemiological and clinical studies. Our primary specific aims are: (1) To assess diet, especially soy intake, in relation to mammographic density. In addition, we will assess the potential modifying and/or confounding effect of dietary factors such as dietary fat, fiber, carotenoids, cruciferous vegetables/isothiocyanates, on the soy-mammographic density association. (2) To assess whether genotypes modify the associations between dietary factors (such as soy intake) and mammographic density. For example, we will evaluate whether the associations between estrogen metabolizing genes (e.g., HSD17B1, CYP1B1, COMT, SULT1A1) and mammographic density are stronger among low soy consumers. Our secondary specific aims are: (3) To assess genotypes of a panel of sex-steroid hormone metabolism genes, in relation to mammographic density. (4) To assess genotypes of other mitogenesis-related genes including the angiotensin I-converting enzyme (ACE), transforming growth factor beta-1(TGFbeta-1), insulin-like growth factor- I (IGF-1) and IGF binding protein (BP)-3), in relation to mammographic density.
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