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：
9982835
负责人：
Scarlett L Gomez
金额：
$ 13.45万
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/9982835
关键词：
Address Adult African African American 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 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 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) 男性的前列腺癌 (PCa) 发病率和死亡率最高众所周知，美国种族/族裔群体患有更具侵袭性的高风险疾病，尤其是慢性疾病。较高的格里森评分和 PSA 水平并不是造成 AA 男性 PCa 高负担的因素。众所周知，AA 面临着相当高水平的社会压力，例如机构和人际压力。歧视、犯罪、社会经济地位低下、社会孤立和资源匮乏的环境。压力源存在于多个层面，从个人到社区再到机构，贯穿生命历程，导致 AA 男性经历的慢性压力可能是造成这种情况的一个因素。我们将应用最近开发的多级框架来应对侵袭性 PCa 的发展和高死亡率。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”导致生物脆弱性，特别是 AA 男性中 PCa 的高负担。目标是： 1) 检查暴露于邻里社会压力源与风险之间的关联在基于人群的样本中，AA 和非西班牙裔白人 (WH) 男性的侵袭性 PCa 和死亡率。在 RESPOND 服务区的所有 AA (N=149,000) 和 WH (N=668,000) 诊断患有 PCa 的男性中，我们将连接有关种族隔离、种族构成、社会剥夺等方面的地理空间数据癌症登记数据的社会和建筑环境属性，并检查这些属性之间的关联 2）检查暴露之间的关联在 10,000 名 AA 男性中，生命历程中的多层次社会压力源以及侵袭性前列腺癌的风险响应。每个压力源将在选定的时间点（早期、中期、 3) 检查多层次社会暴露之间的关联生命历程中的压力源和遗传因素，以及它们与相关因素的综合影响更具体地说，我们将评估多层次社会压力源与以下因素之间的关联： a) 非洲遗传血统的比例，b) 体细胞特征的频率和类型，以及 c) 是否具有社会性压力源、种系遗传学（包括 PCa 侵袭性位点）和体细胞特征与风险共同相关为了实现这些目标，我们设计了一项涉及横断面、前瞻性和回顾性设计，整合来自多个来源（包括癌症）的多级数据登记、患者调查、地理空间（以描述社区层面的压力源）和公共记录数据（以构建成人居住史）、项目 2 的种系遗传学和项目的体细胞肿瘤概况数据 3. 覆盖 6 个州和 1 个大都市区，占美国所有患有 PCa 的 AA 男性的 38%， RESPOND 将代表研究 AA 男性侵袭性 PCa 的单一最大的协调研究工作，其中项目 1 的创新重点是与该人群最相关的社会压力源暴露。