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

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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.