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

摘要-项目1 非洲裔美国人(AA)男性的前列腺癌(PCA)发病率和死亡率是所有男性中最高的 美国的种族/民族群体。众所周知，他们还会患上更具侵袭性的高危疾病，尤其是 Gleason评分和PSA水平较高。导致AA男性自控镇痛负担高的因素不是 为人所知。AA暴露于相当高水平的社会压力，如制度和人际关系 歧视、犯罪、社会经济地位低下、社会孤立和资源贫乏的环境。这些社交媒体 压力源存在于多个层面，从个人到社区再到机构，以及整个生命过程， 导致慢性压力。因此，AA男性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框架， 强调对“细胞接触社会”的考虑和评估，以了解“压力是如何产生的”。 在皮肤下“造成生物脆弱性，特别是在AA男性中，PCA的高负担。我们的特定 目的是：1)检查暴露于邻里社会压力源和 AA和非西班牙裔白人(WH)男性的侵略性前列腺癌和死亡率。在基于总体的样本中 在响应性集水区所有确诊为前列腺癌的AA(N=149,000)和WH(N=668,000)男性中，我们 将连接有关种族隔离、种族构成、社会经济贫困和其他方面的地理空间社区数据 社会和建筑环境属性与癌症登记数据，并检查它们之间的关联 邻里因素与侵袭性PCA和死亡风险；2)检验暴露之间的联系 年10,000名AA男性生命周期多层次社会压力源与攻击性PCA风险的关系 请回答。每个应激源将被单独和组合检查，并针对选定的时间点(早期、中期、 成人生活)，并随时间累积；3)检查接触多层次社会环境之间的联系 整个生命过程中的压力源和遗传因素，以及它们与 咄咄逼人的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)非洲遗传血统的比例，b)体型分布的频率和类型，以及c)是否具有社会性 应激源、生殖系遗传学(包括PCA攻击性基因座)和体型特征与风险共同相关 侵袭性疾病。为了达到这些目标，我们设计了一项多层次的研究，涉及横断面、 前瞻性和追溯性设计，集成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(以表征邻里层面的压力源)和公共记录数据(至 构建成人住宅史)、项目2中的生殖系遗传学和项目中的体细胞肿瘤概况数据 3.覆盖6个州和1个大都市区，占美国所有患有前列腺癌的AA男性的38%， RESPONSE将代表着研究AA男性攻击性PCA的最大规模的协调研究努力， 项目1的创新重点是与这一人群最相关的社会应激源暴露。

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.