DIETARY AND GENETIC DETERMINANTS OF MAMMOGRAPHIC DENSITY

描述（由申请人提供）：乳腺摄影密度目前被认为是乳腺癌风险的最佳替代终点。然而，乳腺摄影密度的决定因素还没有很好地理解。年龄、绝经状态、体型和产次共同解释的乳腺摄影密度总变异不到一半。这项拨款申请的主要目标是跟进我们之前关于乳房X光检查密度的饮食和遗传决定因素的线索。我们建议在新加坡的2，200名绝经后中国妇女中进行一项具有成本效益的横断面研究，这些妇女都是新加坡中国健康研究（一项癌症前瞻性队列研究）和全国性乳房X线摄影筛查计划的参与者。作为进入队列研究的一部分，这些女性接受了面对面的采访，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2，200名妇女的血液样本（用于基因分型）和乳房X线照片已经可用。我们建议使用我们开发的计算机辅助方法来评估乳腺摄影密度，并已成功地应用于流行病学和临床研究。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腺X线摄影密度的关系。此外，我们还将评估膳食因素（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-乳腺摄影密度关联的潜在修饰和/或混杂效应。(2)评估基因型是否改变饮食因素（如大豆摄入量）和乳腺摄影密度之间的关联。例如，我们将评估雌激素代谢基因（例如，HSD 17 B1、CYP 1B 1、COMT、SULT 1A 1）和乳房X线摄影密度在低大豆消费者中更强。我们的第二个具体目标是：（3）评估一组性类固醇激素代谢基因的基因型，与乳腺摄影密度的关系。(4)评估其他有丝分裂相关基因（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- I（IGF-1）和IGF结合蛋白（BP）-3）的基因型与乳腺摄影密度的关系。

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.