DIETARY AND GENETIC DETERMINANTS OF MAMMOGRAPHIC DENSITY

乳房X光密度的饮食和遗传决定因素

• 批准号: 7036517
• 负责人: ANNA H. WU
• 金额: $ 38.99万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036517
• 关键词: Chinese; Cruciferae; binding proteins; carotenoids; clinical research; cost effectiveness; density; dietary fiber; dietary lipid; genotype; hormone metabolism; human subject; insulinlike growth factor; isothiocyanates; mammography; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrient intake activity; nutrition related tag; peptidyl dipeptidase A; postmenopause; soybeans; steroid hormone; transforming growth factors; women' s health

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.

描述（由申请人提供）：乳房X光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线照相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乳房X光密度总变异的不到一半。这项拨款申请的主要目的是跟进我们之前关于乳房X线照相密度的饮食和遗传决定因素的线索。我们建议对新加坡 2,200 名绝经后华人女性进行一项具有成本效益的横断面研究，她们是新加坡华人健康研究、癌症前瞻性队列研究和全国乳房 X 光检查计划的参与者。作为队列研究的一部分，这些女性接受了亲自采访，提供了详细的生活方式信息，并完成了经过验证的 165 项食物频率调查问卷。这 2,200 名女性已经获得了血液样本（用于基因分型）和乳房 X 光检查。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光密度的关系。此外，我们将评估饮食因素（例如膳食脂肪、纤维、类胡萝卜素、十字花科蔬菜/异硫氰酸盐）对大豆-乳房X光密度关联的潜在改变和/或混杂影响。 (2) 评估基因型是否改变饮食因素（例如大豆摄入量）与乳房X线密度之间的关联。例如，我们将评估雌激素代谢基因（例如 HSD17B1、CYP1B1、COMT、SULT1A1）与乳腺 X 光密度之间的关联在低大豆消费人群中是否更强。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线照相密度的关系。 (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（TGFβ-1）、胰岛素样生长因子-I（IGF-1）和IGF结合蛋白（BP）-3）与乳房X光密度的关系。