Neighborhood redlining, economic deprivation, and the breast tumor epigenome: bridging social and molecular epidemiology to address the Black-White breast cancer mortality disparity

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Significance. Although national and philanthropic efforts have sought to reduce and eliminate breast cancer (BC) mortality disparities over the past few decades, they have not only persisted—but widened. Additionally, our knowledge about drivers of race mortality disparities in estrogen receptor–positive (ER+) disease are limited, despite ER+ tumors representing ~70% of BC diagnoses. One potential mechanism driving disparities is a higher rate of de novo or acquired resistance to endocrine therapy among Black women, which can be precipitated by higher levels of psychosocial stress, pro-inflammatory cytokines, and activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Social stressors emanating from discriminatory policies (such as redlining) have the capacity to become biologically embedded in the epigenome of the breast tumor, altering prognosis. These mechanisms, at the intersection of social and molecular epidemiology, have never before been explored. Innovation. Our proposal is innovative in that it will be the first to examine the breast tumor epigenome as a mechanism linking economic deprivation (stemming from housing discrimination) to adverse breast cancer outcomes. Approach. This study will leverage the Georgia Cancer Registry to identify, recruit, and ascertain residential and economic history from Black and White postmenopausal women diagnosed with ER-positive stage I–III BC (2013–2017) in metro-Atlanta and followed for up to 12 years. We will estimate the association between area-level economic deprivation (Aim 1, N=4,433), individual-level economic deprivation (Aim 2, n~1,750) and BC outcomes exploring potential heterogeneity by race. We will examine the extent to which individual-level economic deprivation perturbs the DNA methylome using whole epigenome analyses (Aim 3, n~750). Impact. The results of this study will highlight the potential mechanism by which persistent structural biases perpetrated by government and financial institutions impact breast cancer outcome disparities. We posit that persistent housing discrimination contributes to area- and individual-level economic deprivation over the life- course, resulting in altered inflammatory and endocrine response. Establishing a biological background for BC disparities stemming from housing discrimination will provide new insights into how socio-contextual factors drive cancer disparities by place and race. This research will ultimately advance our understanding of the policy changes needed to advance health equity and, in parallel, will facilitate the prioritization of pharmacologic or behavioral interventions at the individual level.