Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome

As a growing number of studies reveal that racial and ethnic minorities are at an increased risk of developing and dying from various acute and chronic diseases, it is increasingly evident that research must be conducted that will reveal the molecular basis of health disparities. Health inequities often reflect social inequities and exploring the complex relationship between exposures to adverse social factors and their biological consequences is imperative. Our group has shown that place-based measures of structural racism (i.e. redlining) have been associated with an increase in breast cancer mortality. We hypothesized that exposure to adverse inequities may drive epigenetic perturbations that affect racial disparities in breast cancer outcomes. Here, I examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue. My results showed that contemporary redlining is associated with differential methylation in 5 CpG sites. All genes are implicated in breast carcinogenesis, including genes related to inflammation, immune function, and stress response. Further exploration of the top 25 CpG sites, identified interaction of 2 sites by ER status and 1 site was associated with all-cause mortality. In addition, contemporary redlining is associated with epigenetic age acceleration and age acceleration is slightly associated with all-cause mortality. These results identify novel associations between contemporary redlining and the breast tumor DNA methylome. These data are the first to show that structural racism impacts the breast tumor epigenome and provide a strong foundation for further study into how socio-structural determinants “above the skin” influence biological mechanisms “under the skin” and drive disparities. This work will provide new molecular mechanistic insights governing breast cancer disparities and has broader implications for pharmacological treatments and policy interventions that would contribute to the ultimate goal of achieving health equity.