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.

项目概要/摘要 意义虽然国家和慈善事业一直在努力减少和消除乳腺癌。 (BC) 过去几十年来，死亡率差异不仅持续存在，而且还在扩大。 我们对雌激素受体阳性（ER+）疾病种族死亡率差异驱动因素的了解有限， 尽管 ER+ 肿瘤占 BC 诊断的约 70%，但造成差异的一个潜在机制是较高。 黑人女性对内分泌治疗的新发或获得性耐药率，这可能是由于 更高水平的社会心理压力、促炎细胞因子和核因子-κ B 的激活 (NF-κB) 信号通路源自歧视性政策（如红线）。 能够在生物学上嵌入乳腺肿瘤的表观基因组，从而改变预后。 社会流行病学和分子流行病学交叉的机制以前从未被探索过。 创新。我们的提议是创新的，因为它将是第一个将乳腺肿瘤表观基因组作为一种方法进行检查的提议。 将经济剥夺（源于住房歧视）与不利乳腺癌联系起来的机制 本研究将利用佐治亚州癌症登记处来识别、招募和确定结果。 被诊断为 ER 阳性的黑人和白人绝经后妇女的居住史和经济史 我们将在亚特兰大都会区进行 I-III BC 阶段（2013-2017）并跟踪长达 12 年。 地区层面的经济剥夺（目标 1，N=4,433）和个人层面的经济剥夺（目标 2，N=4,433）之间 n~1,750）和 BC 课程探讨种族的潜在异质性。 使用整个表观基因组分析，个人层面的经济剥夺会扰乱 DNA 甲基化组（目标 3， n~750）。这项研究的结果将突出持久结构的潜在机制。 我们认为政府和金融机构的偏见会影响乳腺癌结果的差异。 持续存在的住房歧视导致地区和个人一生中的经济剥夺 当然，导致炎症和内分泌反应改变，从而建立 BC 的生物学背景。 住房歧视引起的差异将为社会背景因素如何驱动提供新的见解 这项研究最终将增进我们对政策的理解。 促进健康公平所需的变革，同时将有助于确定药物或药物的优先顺序 个人层面的行为干预。