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

基本信息

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
项目类别：
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

项目摘要

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光密度，描述乳房中上皮组织和基质组织与脂肪组织的比例，是乳腺癌的一个很强的危险因素。许多已知的乳腺癌危险因素也与乳房X线照相密度，表明乳房X线照相密度是一个重要的中间表型研究。事实上，作为与所有乳腺癌亚型相关的连续且更精确的结果，乳房 X 光检查密度已被证明是乳腺癌的重要替代标志物，并且有人认为乳房X光检查密度是一个更有意义的生物学研究结果。乳腺癌是西班牙裔最常见的癌症，也是导致癌症相关死亡的主要原因居住在美国的女性。最近的一项研究估计，在西班牙裔女性中，乳房密度占 35% 的绝经前乳腺癌和 13% 的绝经后乳腺癌。然而，绝大多数迄今为止，已在非西班牙裔白人中进行了乳房 X 光密度研究，留下了大量我们对不同种族/族裔群体的乳房X光密度及其决定因素的理解存在差距。我们提议对西班牙裔人群进行最大规模的乳房X光密度流行病学研究迄今为止居住在美国的女性。我们将首先在多站点内建立一个包含 3,200 张乳房 X 光照片的存储库美国西班牙裔社区健康研究/拉丁裔研究 (HCHS/SOL) 队列并获得密集区域的估计，非致密面积和百分比密度表型（目标 1）。然后我们将评估社会文化、生殖和总样本量为 6,347，肥胖相关因素与乳房 X 光密度表型相关美国西班牙裔女性（目标 2），利用 HCHS/SOL 中丰富的生活方式和遗传数据以及已经来自 Mountain Park 健康中心 (MPHC) 的现有乳房 X 光密度、生活方式和遗传数据乳房 X 光检查和拉丁裔学习密度 (LLEAD) 研究，其中包括 3,147 名美国西班牙裔女性。最后，我们将进行乳房X光密度表型的遗传关联研究，包括基因组- 我们对 3,300 名女性进行了广泛关联研究 (GWAS)，我们拥有这些女性的 GWAS 和乳房 X 光密度数据。新基因座将在 2,000 名西班牙裔女性的独立群体中进行复制，并评估她们的情况在包含 4,500 例病例和 9,000 例对照的西班牙裔 GWAS 中，研究发现该结果与乳腺癌风险存在关联（目标 3）。 HCHS/SOL 代表多个西班牙裔背景群体（多米尼加人、中美洲人、古巴人、墨西哥人、波多黎各人、南美人），反映了生活在美国的西班牙裔人的多样性。我们的乳房X光检查存储库将构成西班牙裔人口中最大、最全面的乳房 X 光照片集合已经收集了丰富的生活方式和遗传数据。未来的许多项目都将建立在这一独一无二的基础上资源包括收集纵向乳房X光照片以研究密度随时间的变化。随着日益增长的居住在美国的西班牙裔人数，我们需要将流行病学研究扩展到以下风险因素：乳腺癌等常见疾病，以实现跨种族/族裔群体的平等护理。