Genomic Diversity of Prostate Cancer Across the African Diaspora

非洲侨民前列腺癌的基因组多样性

• 批准号: 10548218
• 负责人: TIMOTHY R REBBECK
• 金额: $ 128.49万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-07 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548218
• 关键词: Address; Affect; Africa; Africa South of the Sahara; African; African American; African ancestry; Age; American; Biological; Biological Factors; Cancer Etiology; Caribbean region; Characteristics; Clinical; Clinical Data; Critical Care; Data; Data Set; Development; Diagnosis; Disease; Disease Management; Disparity; Early Diagnosis; Ensure; Environmental Risk Factor; Epidemiology; Ethnic Origin; Ethnic Population; Etiology; European; European ancestry; GENIE; Gene Expression; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genomics; Germ-Line Mutation; Histopathology; Incidence; Inequity; Infrastructure; Inherited; International Agency for Research on Cancer; Knowledge; Location; Malignant Neoplasms; Malignant neoplasm of prostate; Minority Groups; Modeling; Molecular; Molecular Profiling; Mutation; Obesity; Pathogenicity; Pathologic; Pathology; Population; Prevalence; Prevention; Prostate; Prostate carcinoma; Prostatic Neoplasms; Public Health; Race; Research; Resources; Risk; Risk Factors; Risk Management; Sampling; Source; Susceptibility Gene; The Cancer Genome Atlas; cancer genetics; cancer genomics; cancer health disparity; cancer risk; cancer therapy; epidemiologic data; ethnic diversity; experience; genetic risk assessment; genetic variant; genomic data; health care availability; improved; innovation; men; modifiable risk; molecular subtypes; mortality; polygenic risk score; predictive modeling; public database; racial disparity; racial diversity; racial population; social; social health determinants; transcriptome; transcriptomics; treatment strategy; tumor; tumor progression

PROJECT SUMMARY/ABSTRACT African descent men (ADM) across the African diaspora have the highest rates of prostate cancer (CaP) of any racial or ethnic group. The incidence rate in African American men (AAM) is 71% higher than in European American men (EAM) and the AAM mortality rate is 210% higher than EAM. Despite the public health implications of these observations, the underlying causes of this disparity remain unresolved. There is substantial evidence that social inequities and access to health care are in part responsible for CaP disparities. There is limited consistent evidence for exposures and environmental factors in CaP etiology or progression. In contrast, CaP is strongly influenced by inherited genetic variation, and there is growing evidence that the mutational landscape of prostate tumors varies substantially by race. These observations suggest that biological factors influence CaP incidence and tumor aggressiveness differentially by race and may in part explain CaP disparities by race. To inform the biological basis of CaP disparities that adversely affect ADM, we have developed a large, multicenter consortium known as “Men of African Descent and Carcinoma of the Prostate” (MADCaP). Using the resources of this consortium, we propose to undertake a study of CaP in ADM to address the following Aims: Aim 1: Identify common genetic variants associated with CaP aggressiveness in ADM; Aim 2: Define histopathological commonalities of prostate tumors in ADM; and Aim 3: Evaluate molecular signatures and subtypes in prostate tumors and determine their relationship to pathological and clinical characteristics in ADM. The proposed research will have innovative impact in a number of ways. We will address the critical need for increased ethnic diversity in cancer genomics data, which to date has been dominated by studies in European ancestral populations. Ethnically diverse genetic data will not only improve our understanding of genomic contributors to cancer etiology and disparities but will also aid in the development and implementation of cancer genomic analysis for all populations, reduce the potential for errors in determining pathogenicity of genetic susceptibility variants, and improve interpretation of cancer risk in all populations including AAM. In undertaking this research, we will enhance infrastructure needed to undertake genomics research in Africa that includes a large, well-annotated sample of systematically collected tumors with clinical and epidemiologic data that can be used to address a variety of research and clinical questions. We have constructed the MADCaP resources to integrate directly with existing publicly available databases, such as TCGA/ICGC and GENIE, to ensure the African data can be readily compared with data from other sources. Our data will also include deep pathology, clinical and risk factor annotation, largely unavailable in current public datasets, to provide a fuller potential to understand underlying disparities in CaP etiology.

项目总结/摘要 非洲裔男性（ADM）在非洲侨民中前列腺癌（CaP）的发病率最高， 任何种族或民族。非裔美国人（AAM）的发病率比欧洲人高71%。 美国男性（EAM）和AAM的死亡率比EAM高210%。尽管对公共卫生有影响 在这些意见中，造成这种差异的根本原因仍未得到解决。 有大量证据表明，社会不平等和获得医疗保健是CaP的部分原因 差距。在CaP病因学中暴露和环境因素的一致性证据有限， 进展相反，CaP受到遗传变异的强烈影响，越来越多的证据表明， 前列腺肿瘤的突变景观因种族而异。这些观察提示 生物学因素影响不同种族的CaP发病率和肿瘤侵袭性， 按种族解释CaP差异。 为了告知对ADM产生不利影响的CaP差异的生物学基础，我们开发了一个大的， 多中心联盟称为“非洲裔男性和前列腺癌”（MADCaP）。使用 我们建议就行政管理范畴内的电脑辅助程式进行研究，以达致以下目的： 目的1：确定与ADM中CaP侵袭性相关的常见遗传变异;目的2：定义 ADM中前列腺肿瘤的组织病理学共性;以及目标3：评估分子特征， 前列腺肿瘤的亚型，并确定其与ADM的病理和临床特征的关系。 拟议的研究将在许多方面产生创新影响。我们将满足 癌症基因组学数据中种族多样性的增加，迄今为止，欧洲的研究占主导地位。 祖先的人口种族多样性的遗传数据不仅会提高我们对基因组的理解， 癌症病因学和差异的贡献者，但也将有助于癌症的发展和实施 所有人群的基因组分析，减少了在确定遗传致病性方面的错误可能性。 易感性变异，并改善包括AAM在内的所有人群中癌症风险的解释。开展 这项研究，我们将加强在非洲进行基因组学研究所需的基础设施，包括 系统收集大量注释良好的肿瘤样本，并提供临床和流行病学数据， 用于解决各种研究和临床问题。我们已经构建了MADCaP资源， 直接与现有的公开数据库（如TCGA/ICGC和GENIE）集成，以确保 非洲的数据很容易与其他来源的数据进行比较。我们的数据还将包括深层病理学， 临床和风险因素注释，在当前的公共数据集中基本上不可用，以提供更充分的潜力， 了解CaP病因学的潜在差异。