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线学密度目前被认为是我们乳腺癌风险的最佳替代终点。但是，乳房X线学密度的决定因素尚不清楚。年龄，绝经状态，身体大小和奇偶校验总共解释了乳房X线摄影密度总差异的一半。该赠款应用的主要目的是跟进我们先前关于乳房X线摄影密度的饮食和遗传决定因素的潜在客户。我们建议对新加坡的2,200名绝经后中国妇女进行一项具有成本效益的横断面研究，这些妇女既是新加坡中国卫生研究，一项前瞻性癌症研究和全国乳房X线摄影筛查计划的参与者。作为参加队列研究的一部分，这些妇女亲自接受了采访，并提供了详细的生活方式信息，并完成了经过验证的165个项目食品频率问卷。这2200名女性已经可以使用血液标本（用于基因分型）和乳房X线照片。我们建议使用我们开发并成功地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。我们的主要特定目的是：（1）评估与乳房X线摄影密度有关的饮食，尤其是大豆摄入量。此外，我们将评估饮食因素的潜在修饰和/或混杂作用，例如饮食脂肪，纤维，类胡萝卜素，十字花科蔬菜/异硫氰酸酯，对大豆摄影密度关联。 （2）评估基因型是否改变了饮食因素（例如大豆摄入量）和乳房X线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HSD17B1，CYP1B1，COMT，SULT1A1）和乳房X线X摄影密度之间的关联是否在低大豆消费者中更强。我们的次要特定目的是：（3）评估与乳房X线摄影密度有关的一系列性甾体激素代谢基因的基因型。 （4）评估其他与有丝分裂相关的基因的基因型，包括血管紧张素I-转换酶（ACE），转化生长因子β-1（TGFBETA-1）（TGFBETA-1），胰岛素样生长因子I（IGF-1）（IGF-1）和IGF结合蛋白（BP） - 3），与哺乳动物密度相关。