Epigenetic Aging Differs By Race, Subtype and Social Vulnerability Index in Breast Cancer Patients

Purpose: Although breast cancer (BrCa) disparities by age of onset, subtype and mortality are well recognized between Black and White women, the underlying causes remain unknown. We were interested in the impact of methylation on racial disparities, BrCa subtypes and social vulnerability index (SVI). Methods: A whole-genome methylation array was used with DNA extracted from blood samples from women diagnosed with BrCa. After quality control, 158 BrCa patients were included. The biological age and epigenetic age acceleration, defined as the residual from regressing chronological and biological age, were computed using Horvath and GrimAge clocks. The association with aging for the independent factors of self-reported race, BrCa molecular subtypes (ER and HER2), and SVI were evaluated with Mann-Whitney tests and linear regression models. Statistical significance was defined as a P value <0.05. Results: Nearly one-third of our sample were self-reported Black women (28.8%) and the overall mean age at diagnosis was 57.8 years ±11.6. The proportion of women diagnosed with ER− and HER2+ BrCa was 43.6% (N = 68) and 14.7% (N = 23), respectively. Overall, the mean age acceleration is estimated as 2.41 years greater for Black women compared to White women by the GrimAge clock (P = 0.005), and 0.87 years for the Horvath clock (P = 0.52). Among ER- BrCa subtypes, Black women had an average biological age of 1.68 years greater than White women (P = 0.24). Similarly, among HER2+ BrCa, the biological age for Black women was 2.62 years older than White women (P = 0.14). In addition, the SVI median stratified analysis identified a 1.24-year increased age difference for Black women compared to White women in the upper SVI. In the lower SVI stratified analysis, the biological age for Black women was 0.67 years younger than White women. Conclusions: Our analysis identified statistically significant epigenetic age acceleration differences between self-reported Black and White BrCa patients. Both stratified analyses by BrCa subtype and SVI yielded biological age differences by self-reported race, however, directional effects differed based on strata. Although our sample size is limited, our stratified analysis revealed novel research directions to better understand racial disparities in BrCa.