||1R01CA263770-01A1 Interpret this number
||Systemic Racism and Biological Embodiment of Risk in Breast Cancer Mortality
Black women experience much higher breast cancer mortality than any other race/ethnic group in the US.
Despite extensive investigation, the known causes to date do not adequately explain this mortality gap. Largely
missing in the disparities literature is a rigorous examination of systemic racism – i.e., how exposure to an
overarching environment of systemic racism (SR) might impact breast cancer outcomes in Black women.
Multiple lines of evidence, when considered together, indicate this exposure merits investigation. SR (e.g.,
perceived discrimination, residential segregation) is associated with a range of adverse health effects in
Blacks, and chronic psychosocial stress due to SR can become embodied via hyperactivation of the
hypothalamic pituitary adrenal (HPA) axis, leading to inflammatory, metabolic and epigenetic dysregulation.
Thus, we hypothesize that exposure to SR leads to alterations in key biological pathways, which in turn
contribute to excess breast cancer mortality in Black women. No empirical study has directly tested this
hypothesis in a single cohort. To address this gap, we will generate a new prospective cohort with 2,498
incident breast cancer and 2,678 sub-cohort random sample from two parent cohorts -- the REasons for
Geographic and Racial Differences in Stroke (REGARDS) and Southern Community Cohort Study (SCCS)
cohorts. Both parent cohorts over sampled Blacks and include participants from southern states with a history
of SR and obtained extensive baseline and biomarker data, enabling us to measure biomarkers of
inflammation and metabolic dysregulation. We will newly assess measures of SR at the structural and
interpersonal levels and characterize epigenome-wide DNA methylation profiles. Our study will conduct the first
thorough prospective evaluation of the distinct influence of SR, above and beyond other racially pattered risk
factors, on breast cancer disparities in a large, diverse cohort. By quantifying the distinct impact of SR on
breast cancer mortality, and identifying pathways and biomarkers that mediate this association, our study will
help improve the poor accuracy of breast cancer prognostic models in Black women, and inform primary
prevention strategies focused on mitigating SR to reduce racial disparities in breast cancer mortality