Epigenetic Determinants of Racial Disparity in Breast Cancer: Looking beyond Genetic Alterations

SIMPLE SUMMARY: A substantial disparity in breast cancer incidence and mortality exists between African American (AA) and European American (EA) women. However, the basis for these disparities is poorly understood. In this article, we describe that gene–environment interactions mediated through epigenetic modifications may play a significant role in racial disparities in BC incidence and outcomes. Our in silico analyses and an in-depth literature survey suggest that there exists a significant difference in epigenetic patterns between AA and EA women with breast cancer. Herein, we describe the environmental factors that contribute to these epigenetic changes, which may underlie the disparate racial burden in patients with breast cancer. We suggest that AA women with higher basal epigenetic changes, may have higher pre-disposition to cancer onset, and an aggressive disease course. Pre-existing racial differences in epigenetic profiles of breast tissues raises the possibility of examining these profiles for early diagnosis. ABSTRACT: Breast cancer (BC) is the most commonly diagnosed cancer in women. Despite advancements in BC screening, prevention, and treatment, BC incidence and mortality remain high among African American (AA) women. Compared with European American (EA) women, AA women tend to be diagnosed with more advanced and aggressive tumors and exhibit worse survival outcomes. Most studies investigating the determinants of racial disparities in BC have focused on genetic factors associated with African ancestry. However, various environmental and social stressors over an individual’s life course can also shape racial stratification in BC. These social and environmental exposures result in long-term changes in gene expression mediated by epigenetic mechanisms. Epigenetics is often portrayed as an intersection of socially patterned stress and genetic expression. The enduring nature of epigenetic changes makes them suitable for studying the effects of different environmental exposures over an individual’s life course on gene expression. The role of differential social and environmental exposures in racial disparities in BC suggests varied epigenetic profiles or signatures associated with specific BC subtypes in AA and EA women. These epigenetic profiles in EA and AA women could be used as biomarkers for early BC diagnosis and disease prognosis and may prove valuable for the development of targeted therapies for BC. This review article discusses the current state of knowledge regarding epigenetic differences between AA and EA women with BC. We also discuss the role of socio-environmental factors, including psychosocial stress, environmental toxicants, and dietary factors, in delineating the different epigenetic profiles in AA and EA patients with BC.