Impact of Allostatic Load and Neighborhood Contextual Factors on Breast Cancer in the Women's Health Initiative

妇女健康倡议中的非稳态负荷和社区背景因素对乳腺癌的影响

基本信息

批准号：
10707352
负责人：
Lucile Lauren Adams-Campbell
金额：
$ 36.42万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-20 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10707352
关键词：
Address Biological Biological Factors Biological Markers Biological Process Biology Black race Breast Cancer Risk Factor Cancer Biology Cancer Etiology Cancer health equity Cardiovascular system Cells Chronic Clinical Clinical Data Community Actions Cross-Sectional Studies Data Development Diagnosis Diagnostic Disease Disparity Ethnic Origin Ethnic Population Exhibits Exposure to Health Hispanic Immune Incidence Individual Inequity Inflammatory Intervention Knowledge Latinx Link Literature Long-Term Effects Longterm Follow-up Malignant Neoplasms Mammary Neoplasms Measures Mediating Mediator Metabolic Modeling National Health and Nutrition Examination Survey Neighborhoods Nested Case-Control Study Not Hispanic or Latino Outcome Participant Pathway interactions Phenotype Physiological Prevention strategy Process Prospective cohort Public Health Public Policy Publishing Race Racial Segregation Risk Risk Factors Sampling Sampling Studies Socioeconomic Status Stress Structural Racism System Testing Time Tissues United States Weather Woman Women&apos s Health allostatic load biopsychosocial black women breast cancer diagnosis cancer biomarkers cancer epidemiology cancer prevention cancer risk cohort contextual factors cost deprivation design economic disparity epidemiologic data evidence base experience improved malignant breast neoplasm marginalized population mortality risk neighborhood association novel perceived stress prospective racial population residential segregation response social factors socioeconomics stressor structural determinants triple-negative invasive breast carcinoma tumor

项目摘要

PROJECT SUMMARY/ABSTRACT Non-Hispanic Black (NHB) and Hispanic/Latinx women are disproportionately diagnosed with breast tumor exhibiting more aggressive phenotypes; and NHB women are dying from breast cancer at rates higher than every other racial/ethnic group in the United States (US). Due to structural racism (and its downstream effects), NHB and Hispanic/Latinx women experience more chronic stressors compared to non-Hispanic White (NHW) women. Emerging data, from our group and others, show that social and biologic factors contribute to the development of breast cancers with more aggressive tumor features that lead to the poorer outcomes. Evidence supports allostatic load – a measure of dysregulation across major physiologic systems including metabolic, cardiovascular, and immune/inflammatory systems – as a measure of cumulative physiologic stress and risk factor for adverse health outcomes. Data from a nationally representative sample of US women showed that allostatic load is inversely associated with socioeconomic status (SES) and positively associated with breast cancer among Black women, but not White women. No prior study has prospectively explored the impact of allostatic load and neighborhood contextual factors (simultaneously) on breast cancer in a large, diverse study sample. Here we propose to examine the impact of pre-diagnostic allostatic load score (ALS) and objectively measured neighborhood contextual factors on breast cancer incidence and phenotype in a large, nested case-control study of NHB, NHW, and Hispanic/Latinx participants in the Women’s Health Initiative (WHI). Our central hypothesis is that risk of breast cancer and aggressive tumors are attributable to the impact of higher ALS and socioeconomically deprived and racially segregated neighborhood context. Further, we hypothesize that allostatic load mediates the associations of neighborhood context with breast cancer, which differ by race/ethnicity. Leveraging WHI’s prospective design, rich epidemiologic and clinical data, and long-term follow-up, to test these hypotheses through the following aims: 1) Investigate associations of allostatic load with breast cancer risk and tumor phenotype; 2) Investigate associations of neighborhood contextual factors with breast cancer risk and tumor phenotype; and 3) Evaluate whether independent associations of allostatic load and neighborhood context with breast cancer differ by race/ethnicity. This study will have a high impact by yielding novel, prospective data on the impact of unfavorable neighborhood contextual factors and allostatic load (as an intermediate biological process/mechanism between neighborhood context and health) on breast cancer. Findings from this study will contribute new knowledge about the biological basis of long-term effects of structural racism and utility of ALS as a biomarker of cancer risk. These data are essential to developing evidence-based prevention strategies to improve cancer health equity.

项目概要/摘要非西班牙裔黑人 (NHB) 和西班牙裔/拉丁裔女性被诊断患有乳腺癌的比例不成比例肿瘤表现出更具侵袭性的表型；NHB 女性死于乳腺癌的比例很高由于结构性种族主义（及其原因），该比例高于美国所有其他种族/族裔群体。下游效应），相比之下，NHB 和西班牙裔/拉丁裔女性经历更多的慢性压力源来自我们小组和其他人的新兴数据表明，社会和非西班牙裔白人 (NHW) 女性。生物因素导致乳腺癌具有更具侵袭性的肿瘤特征导致较差结果的证据支持调节负荷——一种衡量失调的指标。主要生理系统，包括代谢、心血管和免疫/炎症系统 – 作为累积生理压力和不良健康结果的危险因素的衡量标准。美国女性的全国代表性样本表明，非稳态负荷呈负相关与黑人女性的社会经济地位（SES）和乳腺癌呈正相关，但之前没有研究前瞻性地探讨了非稳态负荷和白人女性的影响。在大型、多样化的研究样本中（同时）研究背景邻里因素对乳腺癌的影响。在这里，我们建议检查诊断前非稳态负荷评分（ALS）的影响并客观地在大量的乳腺癌发病率和表型中测量了邻里环境因素针对女性健康领域的 NHB、NHW 和西班牙裔/拉丁裔参与者的巢式病例对照研究倡议（WHI）。我们的中心假设是乳腺癌和侵袭性肿瘤的风险是。可归因于较高的 ALS 以及社会剥夺和种族隔离的影响此外，我们勇敢地承认，非稳态负荷可以调节以下因素的关联。乳腺癌的社区背景因种族/民族而异。设计、丰富的流行病学和临床数据以及长期随访，通过以下方式检验这些假设目标如下： 1) 研究非稳态负荷与乳腺癌风险和肿瘤的关系表型；2) 研究邻近环境因素与乳腺癌风险的关联；肿瘤表型；和 3) 评估变稳态负荷和乳腺癌的社区环境因种族/民族而异，这项研究将产生很大的影响。产生有关不利邻里环境因素影响的新颖的前瞻性数据，动态负荷（作为邻里环境和环境之间的中间生物过程/机制）这项研究的结果将贡献有关乳腺癌的新知识。结构性种族主义的长期影响和 ALS 作为癌症风险生物标志物的实用性的基础。数据对于制定基于证据的预防策略以改善癌症健康公平至关重要。