The impact of lifestyle and genetic factors on mammographic density in a cohort of Hispanic women

生活方式和遗传因素对西班牙裔女性群体乳房 X 光密度的影响

• 批准号: 10569013
• 负责人: Sara Lindstroem
• 金额: $ 60.35万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-08 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569013
• 关键词: Adipose tissue; Area; Asian; Biological; Black race; Breast; Breast Cancer Detection; Breast Cancer Risk Factor; Caring; Cause of Death; Central American; Clinical; Collection; Cuban; Data; Disease; Dominican; Enrollment; Epithelium; Ethnic Population; Fatty acid glycerol esters; Female; Future; Genetic; Health; Health Personnel; Hispanic; Hispanic Community Health Study/Study of Latinos; Hispanic Populations; Individual; Joints; Knowledge; Latina; Latina Population; Learning; Life Style; Malignant Neoplasms; Mammographic Density; Mammography; Measures; Menopausal Status; Mexican; Not Hispanic or Latino; Obesity; Outcome; Participant; Pathway interactions; Pattern; Phenotype; Population; Population Heterogeneity; Postmenopause; Premenopause; Puerto Rican; Reproductive History; Research; Resources; Risk Factors; Sample Size; Sampling; Site; South American; Surrogate Markers; Time; Tissues; Woman; anticancer research; breast density; cancer subtypes; cohort; density; epidemiology study; evidence base; genetic association; genetic risk factor; genome wide association study; high body mass index; insight; lifestyle factors; malignant breast neoplasm; non-genetic; novel; racial disparity; racial population; repository; reproductive; social culture

ABSTRACT Mammographic density, which describes the proportions of epithelial and stromal vs. adipose tissue in the breast, is a strong risk factor for breast cancer. Many of known breast cancer risk factors are also associated with mammographic density, suggesting that mammographic density is an important intermediate phenotype to study. Indeed, as a continuous and more precise outcome associated with all breast cancer subtypes, mammographic density has proven an important surrogate marker for breast cancer, and it has been argued that mammographic density is a more meaningful biological outcome to study. Breast cancer is the most common cancer and the leading cancer-related cause of death among Hispanic women living in the US. A recent study estimated that among Hispanic women, breast density accounted for 35% of premenopausal and 13% of postmenopausal breast cancers. Yet, an overwhelming majority of mammographic density research to date has been conducted among non-Hispanic Whites, leaving a substantial gap in our understanding of mammographic density and its determinants across racial/ethnic groups. We propose to conduct the largest epidemiological study of mammographic density among Hispanic women living in the US to date. We will first establish a repository of 3,200 mammograms within the multi-site US Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort and obtain estimates of dense area, non-dense area and percent density phenotypes (Aim 1). We will then assess if sociocultural, reproductive and adiposity-related factors are associated with mammographic density phenotypes in a total sample size of 6,347 US Hispanic women (Aim 2), leveraging rich lifestyle and genetic data in HCHS/SOL together with already existing mammographic density, lifestyle and genetic data from the Mountain Park Health Center (MPHC) Mammography and Latinas LEarning About Density (LLEAD) studies, which include 3,147 US Hispanic women. Finally, we will conduct genetic association studies of mammographic density phenotypes, including genome- wide association studies (GWAS) in 3,300 women for whom we have GWAS and mammographic density data. Novel loci will be replicated in an independent population of 2,000 Hispanic women, and assessed for their association with breast cancer risk in a Hispanic GWAS of 4,500 cases and 9,000 controls (Aim 3). HCHS/SOL represents multiple Hispanic background groups (Dominican, Central American, Cuban, Mexican, Puerto Rican, South American), reflecting the diversity of Hispanics living in the US. Our mammogram repository will constitute the largest, most comprehensive collection of mammograms in a Hispanic population with already collected rich lifestyle and genetic data. Numerous future projects would build on this one-of-a-kind resource including collection of longitudinal mammograms to study change in density with time. With the growing number of Hispanics living in the US, we need to expand our epidemiological research into risk factors of common diseases, such as breast cancer, to achieve equal care across racial/ethnic groups.

抽象的 乳房X线摄影密度，描述了乳房中上皮和基质组织与脂肪组织的比例 是乳腺癌的强大危险因素。许多已知的乳腺癌危险因素也与 乳腺X线摄影密度，表明乳房X线摄影密度是研究的重要中间表型。 实际上，作为与所有乳腺癌亚型相关的连续和更精确的结果，乳房X线摄影 密度已证明是乳腺癌的重要替代标记，有人认为乳房X线摄影 密度是研究更有意义的生物学结果。 乳腺癌是西班牙裔最常见的癌症，也是领先的癌症有关的死亡原因 居住在美国的妇女。最近的一项研究估计，在西班牙裔妇女中，乳房密度占 占绝经前的35％和绝经后乳腺癌的13％。然而，绝大多数 迄今为止在非西班牙裔白人之间进行了乳房X线照相密度研究，留下了大量的 我们对种族/族裔群体乳房X线摄影密度及其决定因素的理解差距。 我们建议对西班牙裔乳腺X线摄影密度进行最大的流行病学研究 迄今居住在美国的妇女。我们将首先在多站点内建立一个3200个乳房X线照片的存储库 美国西班牙裔社区健康研究/拉丁美洲人（HCHS/SOL）队列的研究，并获得密集面积的估计， 非密集区域和密度表型百分比（AIM 1）。然后，我们将评估社会文化，生殖和 肥胖相关因素与乳房X线摄影密度表型有关，总样本量为6,347 美国西班牙裔妇女（AIM 2），在HCHS/SOL中利用丰富的生活方式和遗传数据 来自山地公园健康中心（MPHC）的现有乳房X线摄影密度，生活方式和遗传数据 乳房X线摄影和拉丁裔学习密度（LLEAD）研究，其中包括3,147名美国西班牙裔妇女。 最后，我们将进行乳腺X线摄影密度表型的遗传关联研究，包括基因组 - 对我们拥有GWAS和乳房X线照明密度数据的3,300名女性的广泛关联研究（GWAS）。 新颖的基因座将在2,000名西班牙裔妇女的独立人群中复制，并评估她们的 与乳腺癌的风险相关联，其中有4,500例和9,000例对照的西班牙裔GWA（AIM 3）。 HCHS/SOL代表多个西班牙裔背景团体（多米尼加，中美洲，古巴， 墨西哥，南美洲的波多黎各人），反映了居住在美国的西班牙裔多样性。我们的乳房X线照片 存储库将构成西班牙裔人口中最大，最全面的乳房X线照片 已经收集了丰富的生活方式和遗传数据。未来的许多项目将以这种独一无二的方式为基础 资源包括收集纵向乳房X线照片，以随着时间的推移研究密度变化。随着增长 居住在美国的西班牙裔数量，我们需要将流行病学研究扩展到 诸如乳腺癌等常见疾病，以在种族/族裔群体之间获得平等的护理。