Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Immunity and Stress (RESPOND)

非洲血统男性前列腺癌研究：定义遗传、免疫和压力的作用（RESPOND）

基本信息

批准号：
10759094
负责人：
Christopher Alan Haiman
金额：
$ 7.34万
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 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10759094
关键词：
Address African American African American population African ancestry Area Bioinformatics Biological Biological Factors Biometry Cancer Gene Mutation Cancer Patient Cells Characteristics Clinical Clinical Management Cohort Studies DNA DNA Sequence Alteration Data Databases Development Diagnosis Discrimination Disease Ensure Epithelial Cells Exposure to Frequencies Genetic Genetic Predisposition to Disease Genetic study Genomics Geography Goals Health behavior Immune Immunity Incidence Individual Indolent Inflammation Inflammatory Investigation Life Cycle Stages Life Style Malignant neoplasm of prostate Molecular Neighborhoods Oncogenic PSA screening Pathology Pathway interactions Prevalence Prevention strategy Process Program Research Project Grants Prospective cohort Prostate Prostatic Neoplasms Public Health Recording of previous events Records Research Research Personnel Research Project Grants Resources Risk Risk Factors Role Sampling Scientist Social Environment Sociology Somatic Mutation Stress Subgroup Surveys Susceptibility Gene Time Tumor Tissue Variant anticancer research built environment cell type cohort contextual factors data management design disease prognosis early life adversity epidemiologic data exome sequencing genome wide association study genome-wide high risk improved individualized prevention lifestyle factors men mortality multidisciplinary neoplasm registry non-genetic novel patient stratification perceived stress personalized medicine poor health outcome population based programs prostate cancer risk recruit sample collection segregation social social factors social stress social stressor stressor success synergism treatment choice treatment strategy tumor tumor microenvironment

项目摘要

Abstract – Program Project Overview African American (AA) men have a >60% higher incidence and are more likely to be diagnosed with aggressive PCa than white men. Reasons for the greater burden of aggressive disease in AA men are unknown, but are likely to include a multitude of factors including social factors such as lifetime stress, inherited susceptibility, and tumor-related features such as somatic alterations and local inflammation in the microenvironment. The overarching goal of this Program Project is to uncover the social and biological factors that are related to PCa aggressiveness in AA men. To accomplish this objective, we will establish a large, national, population-based cohort study, RESPOND, (Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Immunity and Social Stress) of 10,000 AA men with incident PCa identified through nine SEER and NPCR U.S. cancer registries from states that include 38% of all AA PCa cases in the U.S.. The cohort will provide comprehensive information on multilevel stressors over the lifecourse such as discrimination, early-life adversity, and neighborhood disorder, including geospatial neighborhood data over time and degree of perceived stress; 2) lifestyle factors and health behaviors; 3) disease-specific factors including PSA screening history and treatment choice; 4) germline DNA to study genetic susceptibility, and 5) tumor block samples for characterization of somatic variation and immune profiling of the tumor microenvironment. No previous study has attempted to obtain information across these domains in a single large sample in order to understand the relative contribution of each and relationships between molecular and non-genetic components. In order to address these goals, we have assembled a multi-disciplinary team of scientists and clinicians with established track records in PCa research. Leveraging the RESPOND resource and investigator expertise, we have designed a Program Project composed of four Projects that are supported by four Cores which are all focused on the central theme of identifying social and biological factors related to PCa disease aggressiveness in AA men. These Projects include: the investigation of multilevel social stressors across the lifecourse in relationship with aggressive PCa (Project 1); genome-wide discovery efforts of germline susceptibility loci for aggressive PCa and examination of the relationship between germline and somatic variation (Project 2); the identification of underlying somatic alterations in PCa tumors and biological pathways that are related to aggressive disease (Project 3); and, a detailed assessment of inflammation in the tumor microenvironment as it relates to PCa aggressiveness in AA men (Project 4). Each of the four Projects address a distinct research domain, however, when studied together, create scientific synergy and a far more comprehensive picture of the major factors that contribute to aggressive PCa in AA men. The information we will discover is likely to have immediate clinical implications in the areas of improved patient stratification and personalized medicine. Hence, this study has broad reaching significance and addresses numerous challenges in the clinical management of PCa in AA men.

摘要 – 计划项目概述非裔美国 (AA) 男性的发病率高出 60% 以上，并且更有可能被诊断为攻击性 AA 男性比白人男性患 PCa 的侵袭性疾病负担更大的原因尚不清楚，但确实如此。可能包括多种因素，包括社会因素，如生活压力、遗传易感性和肿瘤相关特征，例如微环境中的体细胞改变和局部炎症。该计划项目的总体目标是揭示与 PCa 相关的社会和生物因素为了实现这一目标，我们将建立一个大型的、全国性的、以人口为基础的组织。队列研究，RESPOND，（非洲血统男性前列腺癌的研究：定义通过 9 个 SEER 和 10,000 名患有 PCa 的 AA 男性的遗传、免疫和社会压力） NPCR 美国各州癌症登记处包含美国所有 AA PCa 病例的 38%。该队列将提供关于生命历程中多层次压力源的综合信息，例如歧视、早年逆境、邻里混乱，包括一段时间内的地理空间邻里数据和感知压力程度； 2) 生活方式因素和健康行为；3) 疾病特异性因素，包括 PSA 筛查史和治疗选择；4) 用于研究遗传易感性的种系 DNA，以及 5) 用于研究的肿瘤块样本肿瘤微环境的体细胞变异和免疫分析的特征先前没有研究。试图在单个大样本中获取跨这些领域的信息，以便了解每个成分的相对贡献以及分子和非遗传成分之间的关系。为了实现这些目标，我们组建了一个多学科的科学家团队，并建立了利用 RESPOND 资源和研究者的专业知识，我们拥有 PCa 研究的跟踪记录。设计了一个由四个项目组成的项目项目，这些项目由四个核心支持，所有这些核心都专注于确定与 AA 中 PCa 疾病侵袭性相关的社会和生物因素的中心主题这些项目包括：调查整个生命过程中人际关系中的多层次社会压力源。侵袭性 PCa（项目 1）的种系易感位点的全基因组发现工作； PCa和种系与体细胞变异之间关系的检查（项目2）； PCa 肿瘤的潜在体细胞改变以及与侵袭性疾病相关的生物途径（项目 3）；以及与 PCa 相关的肿瘤微环境炎症的详细评估 AA 男性的攻击性（项目 4）。然而，这四个项目各自针对不同的研究领域。当一起研究时，可以产生科学的协同作用，并对影响因素的主要因素有更全面的了解。导致 AA 男性侵袭性 PCa 我们将发现的信息可能会立即产生临床效果。因此，这项研究对改善患者分层和个性化医疗领域具有重要意义。具有广泛的影响意义，并解决了 AA 男性 PCa 临床管理中的众多挑战。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evaluating the transcriptional fidelity of cancer models.

评估癌症模型的转录保真度。

DOI：
发表时间：
2021-04-29
期刊：
影响因子：
12.3
作者：
Peng, Da;Gleyzer, Rachel;Tai, Wen;Kumar, Pavithra;Bian, Qin;Isaacs, Bradley;da Rocha, Edroaldo Lummertz;Cai, Stephanie;DiNapoli, Kathleen;Huang, Franklin W;Cahan, Patrick
通讯作者：
Cahan, Patrick

Expression of ACE2, the SARS-CoV-2 receptor, and TMPRSS2 in prostate epithelial cells.

前列腺上皮细胞中 ACE2、SARS-CoV-2 受体和 TMPRSS2 的表达。

DOI：
发表时间：
2020-04-25
期刊：
影响因子：
0
作者：
Song, Hanbing;Seddighzadeh, Bobak;Cooperberg, Matthew R;Huang, Franklin W
通讯作者：
Huang, Franklin W

Club-like cells in proliferative inflammatory atrophy of the prostate.

前列腺增生性炎症萎缩中的棒状细胞。

DOI：
发表时间：
2023-09
期刊：
影响因子：
0
作者：
Huang, Franklin W;Song, Hanbing;Weinstein, Hannah Nw;Xie, Jamie;Cooperberg, Matthew R;Hicks, Jessica;Mummert, Luke;De Marzo, Angelo M;Sfanos, Karen S
通讯作者：
Sfanos, Karen S