DIETARY AND GENETIC DETERMINANTS OF MAMMOGRAPHIC DENSITY

描述（由申请人提供）：乳房x线摄影密度目前被认为是乳腺癌风险的最佳替代终点。然而，乳房x线摄影密度的决定因素尚不清楚。年龄、绝经状态、体型和胎次共同解释了不到一半的乳房x线摄影密度总变异。这项拨款申请的主要目的是跟进我们之前关于乳房x线摄影密度的饮食和遗传决定因素的线索。我们建议在新加坡2200名绝经后的中国妇女中进行一项具有成本效益的横断面研究，这些妇女既参加了新加坡华人健康研究，一项前瞻性癌症队列研究，也参加了全国乳房x光检查计划。作为进入队列研究的一部分，这些女性接受了亲自采访，提供了详细的生活方式信息，并完成了一份经过验证的165项食物频率问卷。这2200名妇女的血液样本（用于基因分型）和乳房x光检查已经可用。我们建议使用我们开发并已成功应用于流行病学和临床研究的计算机辅助方法来评估乳房x线摄影密度。我们的主要具体目标是：(1)评估饮食，特别是大豆摄入量，与乳房x线摄影密度的关系。此外，我们将评估饮食因素（如膳食脂肪、纤维、类胡萝卜素、十字花科蔬菜/异硫氰酸酯）对大豆-乳房x线摄影密度关联的潜在修饰和/或混淆作用。(2)评估基因型是否改变了饮食因素（如大豆摄入量）与乳腺x线摄影密度之间的关系。例如，我们将评估雌激素代谢基因（如HSD17B1、CYP1B1、COMT、SULT1A1）与乳房x线摄影密度之间的关联是否在低大豆消费者中更强。我们的次要具体目标是：(3)评估一组性类固醇激素代谢基因的基因型，与乳房x线摄影密度有关。（4)评估其他有丝分裂相关基因的基因型，包括血管紧张素I转换酶（ACE）、转化生长因子β -1（tgf β -1）、胰岛素样生长因子-1（IGF-1）和IGF结合蛋白(BP)-3）与乳腺x线摄影密度的关系。

DESCRIPTION (provided by applicant): 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.