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

社区红线、经济剥夺和乳腺肿瘤表观基因组：架起社会和分子流行病学的桥梁，解决黑人与白人乳腺癌死亡率差异

• 批准号: 10688327
• 负责人: Lauren E McCullough
• 金额: $ 53.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10688327
• 关键词: Accounting; Address; Area; Automobile Driving; Behavior Therapy; Biological; Black race; Cessation of life; Clinical; Communities; Cytokine Activation; DNA; DNA Methylation; Data; Diagnosis; Discrimination; Disease; Early Diagnosis; Economics; Effectiveness; Employment; Endocrine; Environment; Estrogen receptor positive; Financial Hardship; Genes; Government; Health Services; Heterogeneity; Housing; Individual; Inflammation; Inflammatory; Inflammatory Response; Institution; Intervention; Knowledge; Life Cycle Stages; Link; Longevity; Malignant Neoplasms; Mammary Neoplasms; Mediator of activation protein; Molecular; Molecular Epidemiology; Molecular Target; NF-kappa B; Neighborhoods; Not Hispanic or Latino; Outcome; Pathway interactions; Pharmacology; Plant Roots; Play; Policies; Population; Postmenopause; Poverty; Prognosis; Psychosocial Stress; Public Health; Race; Recording of previous events; Recurrence; Reporting; Research; Resistance; Role; Services; Signal Pathway; Signal Transduction; Stress; Structural Racism; System; Tumor Subtype; Tumor Tissue; Weather; Woman; aggressive therapy; bead chip; black women; breast cancer diagnosis; breast tumorigenesis; cancer health disparity; cancer recurrence; contextual factors; cytokine; deprivation; epigenome; hazard; health equity; health inequalities; hormone therapy; improved; improved outcome; innovation; insight; malignant breast neoplasm; methylation pattern; methylome; mortality; mortality disparity; neoplasm registry; progenitor; racial difference; racial disparity; recruit; residence; response; segregation; social determinants; social epidemiology; social factors; social stressor; stem; therapy resistant; triple-negative invasive breast carcinoma; tumor; tumor DNA

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.

项目总结/文摘