Project 1: Multilevel Social Stressors and Aggressive Prostate Cancer in African American Men

项目 1：非裔美国男性的多层次社会压力源和侵袭性前列腺癌

• 批准号: 10447153
• 负责人: Scarlett L Gomez
• 金额: $ 18.65万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447153
• 关键词: Address; Adult; African; African American; African American population; African ancestry; Biological; Catchment Area; Cells; Chronic; Chronic Disease; Chronic stress; Communities; Crime; Data; Demography; Development; Diagnosis; Discrimination; Disease; Disease Progression; Disease susceptibility; Environment; Epidemiology; Ethnic Origin; Ethnic group; Evaluation; Exposure to; Fibrinogen; Frequencies; Future; Genetic; Genotype; Gleason Grade for Prostate Cancer; Goals; Household Heads; Housing; Immune; Immunity; Incidence; Individual; Inflammation; Infrastructure; Joints; Life; Link; Malignant neoplasm of prostate; Molecular; Molecular Epidemiology; Neighborhoods; Not Hispanic or Latino; Outcome; PSA level; Patients; Population; Predisposition; Prevention; Public Health; Race; Recording of previous events; Research; Resource-limited setting; Resources; Risk; Risk Factors; Role; Sampling; Skin; Social Environment; Social isolation; Societies; Stress; Surveys; Time; Unemployment; built environment; data registry; deprivation; design; disadvantaged population; disorder risk; early life adversity; experience; follow-up; food environment; genetic epidemiology; high risk; innovation; low socioeconomic status; men; metropolitan; modifiable risk; mortality; mortality risk; multidisciplinary; multiple data sources; neoplasm registry; population based; prospective; prostate cancer risk; racial and ethnic; segregation; social; social adversity; social factors; social health determinants; social stressor; socioeconomics; stressor; tumor; tumor microenvironment; tumor progression; walkability

Abstract – Project 1 African-American (AA) men experience the highest prostate cancer (PCa) incidence and mortality rates of all U.S. racial/ethnic groups. They are also known to present with more aggressive high-risk disease, especially of higher Gleason score and PSA levels. Factors contributing to the high burden of PCa among AA men are not known. AAs are exposed to considerably higher levels of social stressors such as institutional and interpersonal discrimination, crime, low socioeconomic status, social isolation, and resource-poor environments. These social stressors exist at multiple levels, from individual to neighborhood to institutional, and across the lifecourse, leading to chronic stress. Social stressors experienced among AA men may thus be a contributor to the development of aggressive PCa and high mortality. We will apply recently developed multilevel frameworks that emphasize the consideration and evaluation of exposures from “cells to society” to understand how “stress gets under the skin” to cause biological vulnerability, specifically the high burden of PCa among AA men. Our specific aims are: 1) Examine the associations between exposures to neighborhood social stressors and risk of aggressive PCa and mortality among AA and non-Hispanic White (WH) men. Among population-based samples of all AA (N=149,000) and WH (N=668,000) men diagnosed with PCa in the RESPOND catchment areas, we will link geospatial neighborhood data on segregation, racial composition, socioeconomic deprivation, and other social and built environment attributes to cancer registry data and examine the associations between these neighborhood factors and aggressive PCa and risk of mortality; 2) Examine the associations between exposures to multilevel social stressors across the lifecourse and risk of aggressive PCa among 10,000 AA men in RESPOND. Each stressor will be examined individually and combined, and for selected time points (early, mid, adult life) and cumulatively over time; 3) Examine the associations between exposures to multilevel social stressors across the lifecourse and genetic factors, as well as their combined effects in association with aggressive PCa. More specifically, we will assess the association between the multilevel social stressors and: a) proportion of African genetic ancestry, b) frequency and type of somatic profiles, and c) whether social stressors, germline genetics (including PCa aggressive loci), and somatic profiles are jointly associated with risk of aggressive disease. To address these aims, we have designed a multilevel study involving cross-sectional, prospective, and retrospective designs that integrates multilevel data from multiple sources including cancer registry, patient survey, geospatial (to characterize neighborhood-level stressors) and public record data (to construct adult residential history), germline genetics from Project 2 and somatic tumor profile data from Project 3. Covering 6 states and 1 metropolitan region, and representing 38% of all AA men with PCa in the U.S., RESPOND will represent the single largest coordinated research effort to study aggressive PCa in AA men, with an innovative focus in Project 1 on social stressor exposures that are most relevant to this population.

摘要-项目1 非洲裔美国人（AA）男性的前列腺癌（PCa）发病率和死亡率最高 美国种族/民族团体。他们也被称为目前更积极的高风险疾病，特别是 Gleason评分和PSA水平较高。AA男性中导致PCa高负担的因素不是 知道的认可机构所面对的社会压力，例如机构及人际关系等， 歧视、犯罪、社会经济地位低下、社会孤立和资源贫乏的环境。这些社会 压力源存在于多个层面，从个人到社区到机构，跨越生命历程， 导致慢性压力因此，AA男性中经历的社会压力可能是导致 发展为侵袭性前列腺癌和高死亡率。我们将应用最近开发的多层次框架， 强调对“细胞到社会”的暴露的考虑和评估，以了解“压力是如何产生的” 皮肤下的”导致生物脆弱性，特别是AA男性中PCa的高负担。我们的具体 目的是：1）检查暴露于社区社会压力源和风险之间的关联 AA和非西班牙裔白色（WH）男性中侵袭性PCa和死亡率。在基于人口的样本中 在RESPOND集水区诊断为PCa的所有AA（N= 149，000）和WH（N= 668，000）男性中，我们 将把有关种族隔离、种族构成、社会经济贫困和其他方面的地理空间邻里数据联系起来， 社会和建筑环境属性的癌症登记数据，并检查这些之间的关联 邻里因素和积极的PCa和死亡风险; 2）检查暴露之间的关联 在10,000名AA男性中， 回复。每个压力源将单独和组合检查，并在选定的时间点（早期，中期， 成年生活），并随着时间的推移累积; 3）检查暴露于多层次的社会 整个生命过程中的压力源和遗传因素，以及它们与 积极的PCa。更具体地说，我们将评估多层次社会压力源与以下因素之间的关联： a）非洲遗传祖先的比例，B）体细胞概况的频率和类型，以及c）是否社会 应激源、生殖系遗传学（包括PCa侵袭性基因座）和体细胞特征共同与风险相关。 侵袭性疾病的症状为了实现这些目标，我们设计了一项多层次的研究， 前瞻性和回顾性设计，整合了来自多个来源的多水平数据，包括癌症 登记、患者调查、地理空间（以表征社区层面的压力源）和公共记录数据（以 构建成人居住史）、来自项目2的生殖系遗传学和来自项目3的体细胞肿瘤概况数据。 3.覆盖6个州和1个大都市地区，占美国所有患有PCa的AA男性的38%， RESPOND将代表在AA男性中研究攻击性PCa的最大的单一协调研究工作， 项目1的创新重点是与这一人群最相关的社会压力暴露。