R01CA259200

Genomic Diversity of Prostate Cancer Across the African Diaspora - 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 healthcare 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.
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.

Dana-Farber Cancer Institute

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Boston, Massachusetts 022155418 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been extended from 12/31/26 to 04/30/27 and the total obligations have increased 290% from $1,324,467 to $5,164,514.