ABSTRACT Hispanic women have a lower incidence of breast cancer than non-Hispanic white and African American women; however, they are more likely to die from the disease. They are diagnosed at younger ages and have higher rates of high grade and estrogen receptor-negative tumors, which all lead to poorer prognosis. The extent to which genetic and environmental factors play a role in these disparities has not been fully elucidated. The main goal of this proposal is to identify DNA methylation marks in Hispanic women that are associated with breast cancer taking into consideration the racial subgroups of the Hispanic popula- tion. This study will address the following specific aims: 1) determine the association between DNA methylation biomarkers and breast cancer prognostic markers in high-risk Hispanic women, and 2) identi- fy DNA methylation biomarkers of breast cancer in Hispanic women considering ancestry. It will also use ances- try informative markers (AIMs) already identified in the literature to characterize the differential contri- bution of racial backgrounds to DNA methylation biomarkers in this disease. The project will address whether DNA methylation panels (epitypes) used in the classification of breast cancer tumors which have prognostic and treatment potential, can be used in a racially and ethnically diverse cohort of high-risk women. The first aim will focus on whether known current epitypes can identify samples at higher risk of mortality and whether clustering is modified by genetic ancestry. The second aim's goal is to identify breast tumor DNA methylation marks specific to Hispanic women. Both analysis will be carried in breast cancer cases from the New York site of the Breast Cancer Family Registry (BCFR). Using the BCFR is ideal because it has already collected biospecimens and detailed epidemiological data This study will be the first focusing on DNA methylation biomarkers in a population of Hispanic breast cancer cases. The inclusion of ancestry informative markers to determine the admixture substructure of the study population in association with DNA methylation is also novel. This research is expected to aid in the identification of individuals with higher risk of mortality, and ultimately lead to targeted treatments to reduce breast cancer mortality in this population. .

PROJECT NARRATIVE Hispanics are the largest growing minority population in the US and breast cancer is the most common cancer and the leading cause of cancer death among women in this group. While many studies of breast cancer have been carried out, few studies have focused on Hispanic women. This proposal aims to be the first to identify DNA methylation biomarkers that reflect a combined effect of genetic susceptibility and environmental insults in Hispanic women, and ultimately lead to better targeted therapies with the potential of reducing mortality in this population