Systemic Racism and Biological Embodiment of Risk in Breast Cancer Mortality

系统性种族主义和乳腺癌死亡率风险的生物学体现

• 批准号: 10453878
• 负责人: Tomi F Akinyemiju
• 金额: $ 82.45万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10453878
• 关键词: Address; Area; Biological; Biological Markers; Black American; Black Populations; Black race; Breast Cancer Model; Breast Cancer Patient; Breast Cancer Risk Factor; Breast Cancer gene; Cancer Etiology; Cancer Prognosis; Cessation of life; Chronic; Clinical; Cohort Studies; Communities; Crows; DNA Methylation; Data; Diagnostic; Dyslipidemias; Environment; Epigenetic Process; Estrogen receptor negative; Ethnic group; Evaluation; Exposure to; Fibrinogen; Follow-Up Studies; Future; Genes; Genetic; Health; Hyperinsulinism; IL8 gene; Immune; Incidence; Inflammation; Inflammatory; Institutional Racism; Interleukin-10; Interleukin-6; Investigation; Knowledge; Laws; Lead; Legal; Link; Literature; Measures; Mediating; Metabolic; Modeling; Outcome; Parents; Participant; Pathogenesis; Pathway interactions; Patient Self-Report; Patients; Persons; Prevention strategy; Primary Prevention; Process; Prognosis; Prognostic Marker; Prospective Studies; Prospective cohort; Psychosocial Stress; Public Health; Race; Reasons for Geographic And Racial Differences in Stroke; Recording of previous events; Research; Resources; Risk; Risk Factors; Sampling; Socioeconomic Status; Support Groups; Testing; Time; United States; Woman; adverse outcome; base; biological adaptation to stress; black women; breast cancer survival; cancer health disparity; clinically relevant; cohort; comorbidity; data infrastructure; epigenome; experience; hypothalamic-pituitary-adrenal axis; improved; indexing; malignant breast neoplasm; mortality; mortality disparity; mortality risk; multi-ethnic; neoplasm registry; novel; perceived discrimination; prognostic model; prospective; pyrosequencing; racial discrimination; racial disparity; residential segregation; tumor

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

黑人女性的乳腺癌死亡率比美国任何其他种族/族裔群体都要高得多。 尽管进行了广泛的调查，但迄今为止已知的原因并不能充分解释这种死亡率差异。 差异文献中缺少的是对系统性种族主义的严格审查——即，如何暴露于 系统性种族主义（SR）的总体环境可能会影响黑人女性的乳腺癌结局。 综合考虑多种证据，表明这种暴露值得调查（例如，SR）。 感知到的歧视、居住隔离）与一系列不利的健康影响有关 黑人和由于 SR 导致的慢性心理社会压力可以通过过度激活来体现 下丘脑垂体肾上腺 (HPA) 轴，导致炎症、代谢和表观遗传失调。 因此，我们发现暴露于 SR 会导致关键生物途径的改变，从而反过来 导致黑人女性乳腺癌死亡率过高的因素尚无实证研究直接检验过这一点。 为了解决这一差距，我们将生成一个包含 2,498 名新的前瞻性队列。 乳腺癌事件和来自两个父队列的 2,678 个子队列随机样本——原因 中风的地理和种族差异 (REGARDS) 和南方社区队列研究 (SCCS) 两个父母群体都对黑人进行了抽样调查，其中包括来自有历史的南部各州的参与者。 SR 和广泛获得的基线和生物标志物数据，使我们能够测量 我们将重新评估结构和代谢失调的 SR 措施。 我们的研究将首次进行。 对 SR 的独特影响进行全面的前瞻性评估，超越其他种族风险 通过量化 SR 对乳腺癌差异的不同影响。 乳腺癌死亡率，并确定介导这种关联的途径和生物标志物，我们的研究将 帮助改善黑人女性乳腺癌预后模型的低准确性，并为主要患者提供信息 预防策略侧重于减轻 SR，以减少乳腺癌死亡率的种族差异