Investigating Socio-Structural Determinants of Health and the Tumor Epigenome to Understand the Etiology of Racial Disparities in Breast Cancer

研究健康的社会结构决定因素和肿瘤表观基因组，以了解乳腺癌种族差异的病因

• 批准号: 10361020
• 负责人: Jasmine Miller-Kleinhenz
• 金额: $ 9.21万
• 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: 2022-03-11 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10361020
• 关键词: Address; Affect; Air Pollution; Area; Award; Biological; Black race; Breast Cancer Patient; Chronic; Communication; DNA; DNA Methylation; DNA Sequence; Data; Development; Diagnosis; Drug resistance; Education; Environment; Environmental Risk Factor; Epidemiology; Epigenetic Process; Etiology; Exposure to; Fostering; Gene Expression; Genes; Genetic Variation; Goals; Green space; Health; Healthcare; Hematology; Housing; Incidence; Inflammation; Institutes; Intervention; Investigation; Knowledge; Leadership; Learning; Life Style; Link; Location; Malignant Neoplasms; Mammary Neoplasms; Measures; Mentors; Molecular Epidemiology; Neighborhoods; Neoplasm Metastasis; Oncogenic; Oncology; Outcome; Pathology; Pathway interactions; Pharmacological Treatment; Phase; Phenotype; Physical activity; Play; Policies; Population; Positioning Attribute; Prevalence; Psychosocial Stress; Public Health Schools; Publishing; Race; Reporting; Research; Research Personnel; Research Training; Role; Sampling; Signal Pathway; Signal Transduction; Signaling Molecule; Skin; Stress; Structural Racism; Supervision; Tissues; Tobacco smoke; Training; Tumor Biology; Tumor Subtype; Tumor Tissue; Universities; Variant; Woman; Work; aggressive breast cancer; base; bead chip; beta catenin; biobank; black women; cancer health disparity; cancer subtypes; didactic education; disparity reduction; epigenome; experience; health disparity; health equity; malignant breast neoplasm; methylome; mortality; neoplasm registry; nutrition; professional atmosphere; professor; programs; racial disparity; skills; social; social disadvantage; social epidemiology; social factors; social health determinants; social structure; triple-negative invasive breast carcinoma; tumor; tumor DNA; tumorigenesis

Project Summary/ Abstract The overarching goal of this project is to examine how socio-structural determinants of health impact the breast tumor DNA methylome, activation of oncogenic signaling and ultimately, the racially disparate development of triple negative breast cancer (TNBC). The etiologic basis of racial disparities in TNBC is not well understood and few studies have investigated the impact of social determinants of health as potential drivers of disparities. Recent work from the McCullough group shows that, in Atlanta, Black women with breast cancer are more likely to live in redlined neighborhoods than White women (80% vs 20%) and that living in areas with high rates of redlining is associated with a 60% increase in breast cancer mortality. These data support the need to investigate redlining as an etiologic driver of race disparities in TNBC. We posit that to achieve health equity, it is necessary to understand how socio-structural inequities can be adversely manifested biologically, resulting in breast cancer. The goal of this study is to elucidate a biological mechanism that explains the association between neighborhood-level redlining and disparities in TNBC. This investigation requires a researcher with a diverse skillset that can address questions from the population to the bench. This Pathway to Independence Award (K99/R00) application by Dr. Miller-Kleinhenz intends to uniquely position her to answer these questions by building on her prior expertise in breast tumor biology and expanding her skill set in social and molecular epidemiology and epigenetics. To achieve the aims of this research, Dr. Miller-Kleinhenz will focus her training in three areas, (1) increasing knowledge through a comprehensive didactic curriculum, (2) experiencing and learning from varied research environments, and (3) fostering professional development through leadership, scientific communication, and then transitioning to independence. These training goals will be supervised by an interdisciplinary mentoring team, led by Dr. Lauren McCullough, a cancer health disparities and molecular epidemiology expert and an Assistant Professor of Epidemiology at Rollins School of Public Health at Emory University. The co-mentor will be Dr. Adam Marcus, an expert cancer biologist and a Professor of Hematology and Oncology and the Interim Executive Director of the Winship Cancer Institute. This training will aid Dr. Miller-Kleinhenz to pursue the following aims during the K99 phase: Understanding the impact of redlining as a social-structural determinant of health that is associated with TNBC development (Aim 1) and examining redlining-associated DNA methylation signatures of the breast tumor epigenome in TNBC (Aim 2). During the R00 phase, she will determine the pathobiological significance of redlining-associated expression of oncogenic signaling pathways in TNBC (Aim 3). This 5-year research and training plan will allow Dr. Miller-Kleinhenz to establish an independent research program that will elucidate new avenues for policy interventions and pharmacological treatments that would contribute to the ultimate goal of reducing cancer health disparities.

项目摘要/摘要 该项目的总体目标是研究健康的社会结构决定因素如何影响乳房 肿瘤DNA甲基团，致癌信号的激活，最终是种族歧视的发展 三重阴性乳腺癌（TNBC）。 TNBC种族差异的病因学基础尚不清楚 很少有研究调查了健康决定因素作为差异的潜在驱动因素的影响。 McCullough组的最新工作表明，在亚特兰大，黑人乳腺癌的黑人女性更多 比白人妇女（80％vs 20％）生活在红线的社区中，而居住在率高的地区 红线与乳腺癌死亡率增加60％有关。这些数据支持需要 研究红线作为TNBC种族差异的病因学驱动力。我们认为，为了实现健康公平， 必须了解社会结构不平等如何在生物学上表现出不利的表现，从而 在乳腺癌中。这项研究的目的是阐明一种解释关联的生物学机制 在TNBC中的邻居级别的红线和差异之间。这项调查需要一个研究人员 可以解决从人口到替补席的各种技能。独立途径 Miller-Kleinhenz博士的奖项（K99/R00）申请，打算唯一地定位她以回答这些问题 通过建立她先前在乳腺肿瘤生物学方面的专业知识，并扩大了她在社交和分子领域的技能 流行病学和表观遗传学。为了实现这项研究的目的，米勒·克莱恩顿（Miller-Kleinhenz）博士将集中精力 在三个领域，（1）通过全面的教学课程增加知识，（2）体验和 从各种研究环境中学习，（3）通过领导来促进专业发展， 科学交流，然后过渡到独立。这些培训目标将由 由劳伦·麦卡洛（Lauren McCullough）博士领导的跨学科指导团队，癌症健康差异和分子 埃默里（Emory）罗林斯公共卫生学院的流行病学专家和流行病学助理教授 大学。该联合会员将是癌症生物学家兼血液学教授亚当·马库斯（Adam Marcus）博士 和肿瘤学和Winship癌症研究所的临时执行主任。该培训将帮助博士 Miller-Kleinhenz在K99阶段追求以下目标：理解红线的影响 与TNBC开发相关的健康决定因素（AIM 1）并检查 TNBC中乳腺肿瘤表观基因组的红线相关DNA甲基化特征（AIM 2）。在 R00相，她将确定致癌性相关表达的病理学意义 TNBC中的信号通路（AIM 3）。这个为期5年的研究和培训计划将使Miller-Kleinhenz博士能够 建立一个独立的研究计划，该计划将阐明政策干预措施的新途径 有助于降低癌症健康差异的最终目标的药理治疗方法。