Genomic and Biological Risk Prediction of Aggressive and Lethal Prostate Cancer in African American Men
Abstract
Research Plan: Despite robust evidence suggesting African-descent men have a higher risk of dying from prostate cancer compared to other men, clinical tools used to predict prognosis are not currently able to incorporate race to predict which men may be at the highest risk of lethal forms of prostate cancer. As such, clinical tools used to determine prognosis and guide treatment recommendations that have been developed based on studies that have historically underrepresented the African-descent population are still applied to men of African descent. These prognostic tools do poorly in predicting which men of African descent may be most at risk of lethal disease and therefore may contribute to disparities in prostate cancer outcomes. Furthermore, current prognostic tools/nomograms have proven to be suboptimal in predicting the patients with potentially inherently aggressive biology that may be at risk of lethal prostate cancer. To date, there are no specific risk prediction tools that have been developed for men of African descent, and the biology and genomics of prostate cancer in African-descent men is not well characterized. To this end, the purpose of this project is to develop a novel genomic/biological risk prediction approach to prostate cancer in men of African descent by identifying and developing a genomic signature that can predict for aggressive and potentially lethal prostate cancer. This project will utilize rich data from several large data sources and registries to evaluate the impact of genetic biomarkers and other clinical factors on the risk of lethal prostate cancer in men of African descent. The resulting genomic findings could help improve currently used clinical tools to identify African-descent men most likely to be at risk of lethal prostate cancer. The process of this proposed project has minimal risk to patients and has the potential to make an immediate clinical impact within the 2 years of the proposed project. The ability to use genomic information to identify a subset of African-descent men who might have underlying aggressive prostate cancer will enable clinicians to more accurately risk-stratify patients for appropriate treatment recommendations to improve disease control and reduce disparities in prostate cancer outcomes. This project addresses several of the FY18 Prostate Cancer Research Program overarching challenges, including directly defining the biology of lethal prostate cancer in an effort to reduce death and reduce lethal prostate cancer in African-Americans, Veterans, and other high-risk populations. This project was designed around my career research interests, which are to identify and address major contributors to disparities in prostate cancer outcomes and care patterns. My major immediate research goal is to identify new genomic information that can help to identify African-descent men most likely to be at risk of lethal prostate cancer. Ultimately, the potential of this project and my career goal is to reduce the number of disproportionate deaths and suffering that patients of African descent face. As I continue to pursue my research interests in addressing prostate cancer disparities, I have realized that I need to develop critical skills in biomarker development and cancer genetic epidemiology in order to address the aims of this proposal, become an independent translational researcher, and make a significant impact toward understanding the potential biological drivers of prostate cancer disparities. To this end, I have chosen Professor Timothy Rebbeck, a world-renowned disparities cancer genetic epidemiologist, as my mentor. Dr. Rebbeck has directed multiple molecular epidemiologic studies and international consortia to identify and characterize genes that are candidates for involvement in prostate cancer etiology and to describe the relationship of genomics with biochemical or physiological traits, cancer occurrences, cancer outcomes, and cancer dispariti
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910303
Entities
People
- Brandon A Mahal
Organizations
- Dana–Farber Cancer Institute
- United States Army