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

基本信息

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
项目类别：
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

项目摘要

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 非裔美国人（AA）男性经历了所有人的前列腺癌（PCA）发病率最高美国种族/族裔。他们还众所周知，它们会出现更具侵略性的高风险疾病，尤其是更高的格里森评分和PSA水平。 AA男性中有助于PCA高燃烧的因素不是已知。 AAS暴露于考虑更高水平的社会压力源，例如机构和人际关系歧视，犯罪，低社会经济地位，社会隔离和资源贫乏的环境。这些社交压力源在多个层面上，从个人到邻里到机构，以及整个生命之际，导致慢性压力。因此发展积极的PCA和高死亡率。我们将应用最近开发的多级框架强调对从“牢房到社会”暴露的考虑和评估，以了解“压力如何获得在皮肤下“引起生物学脆弱性，特别是AA男士的PCA负担很大。我们的具体目的是：1）检查与邻里社会压力源的暴露与风险之间的关联 AA和非西班牙裔白人（WH）的侵略性PCA和死亡率。在基于人群的样本中在所有AA（n = 149,000）和WH（n = 668,000）的男性中，在响应集水区中被诊断为PCA，我们将链接有关种族隔离，种族组成，社会经济剥夺和其他的地理空间邻里数据社会和建筑环境归因于癌症注册表的数据，并检查这些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整个生命过程中多层次的社会压力源，并在10,000名AA中有侵略性PCA的风险回应。每个压力源将单独和组合检查，以及对于选定的时间点（早期，中，成人生活），随着时间的流逝累积； 3）检查与多层次社会接触之间的关联在整个生命力和遗传因素中的努力及其综合作用与激进的PCA。更具体地说，我们将评估多层社会压力源之间的关联，并： a）非洲遗传血统的比例，b）躯体特征的频率和类型，c）社会是否社会压力源，种系遗传学（包括PCA侵略性语言环境）和躯体特征与风险共同相关侵略性疾病。为了解决这些目标，我们设计了一项涉及横截面的多层次研究，潜在的和回顾性设计，这些设计整合了来自包括癌症在内的多个来源的多层次数据注册表，患者调查，地理空间（以邻里级别的压力源为特征）和公共记录数据（构建成年居民历史），项目2的种系遗传学以及项目的体细胞概况数据 3。覆盖6个州和1个大都市地区，占美国PCA的所有AA男性的38％，响应将代表最大的协调研究工作，以研究AA男子的积极PCA，项目1中的创新重点是与该人群最相关的社会压力源暴露。