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.

摘要 乳房X光摄影密度，它描述了乳房上皮和间质与脂肪组织的比例， 是乳腺癌的一个重要风险因素。许多已知的乳腺癌危险因素也与 钼靶密度，提示钼靶密度是需要研究的重要中间表型。 事实上，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光检查 密度已被证明是乳腺癌的重要替代标记物，而且有人认为乳房X光照相 密度是一个更有意义的生物学结果，值得研究。 乳腺癌是西班牙裔最常见的癌症，也是与癌症相关的主要死亡原因。 生活在美国的女性。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，压倒性的大多数 到目前为止，乳房X光密度研究已经在非西班牙裔白人中进行，留下了大量的 在种族/民族群体中，我们对乳房X光检查密度及其决定因素的理解存在差距。 我们建议在西班牙裔中进行最大规模的乳房X光摄影密度流行病学研究。 到目前为止生活在美国的女性。我们将首先在多个站点内建立一个包含3200个乳房X光片的存储库 美国拉美裔社区健康研究/拉丁裔研究(HCHS/SOL)队列并获得人口稠密地区的估计， 非致密区域和百分比密度表型(目标1)。然后我们将评估社会文化、生殖和 在总样本量为6,347人中，肥胖相关因素与乳房X光摄影密度表型有关 美国西班牙裔女性(目标2)，利用HCHS/SOL中丰富的生活方式和基因数据，以及已经 来自山地公园健康中心(MPHC)的现有乳房X光检查密度、生活方式和基因数据 乳房X光检查和拉丁裔了解密度(LLead)研究，其中包括3147名美国拉美裔女性。 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- 对3300名女性进行了广谱关联研究，我们有广谱关联研究和乳房X光摄影密度数据。 新的基因座将在2000名拉美裔女性的独立人群中复制，并评估其 在由4,500例西班牙裔患者和9,000名对照组成的西班牙裔GWA中，乳腺癌风险的相关性(目标3)。 HCHS/SOL代表多个西班牙裔背景群体(多米尼加、中美洲、古巴、 墨西哥人、波多黎各人、南美人)，反映了生活在美国的拉美裔美国人的多样性。我们的乳房X光检查 资料库将构成拉美裔人口中最大、最全面的乳房X光照片集 已经收集了丰富的生活方式和基因数据。许多未来的项目将建立在这种独一无二的基础上 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。随着不断增长的 居住在美国的拉美裔美国人的数量，我们需要扩大我们的流行病学研究，以探讨 为了实现不同种族/族裔群体之间的平等护理，应加强对乳腺癌等常见病的治疗。