Genetic and Epigenetic Prostate Cancer-Related Alterations in Early Onset Disease in African American Men
Abstract
African American (AA) men are diagnosed with early-onset (</=55 years of age) of prostate cancer (PCa) more often than any other racial/ethnic group. AA men are diagnosed with higher levels of prostate-specific antigen (PSA), higher grade disease at diagnosis, higher tumor volume, and more aggressive disease than any other group. As a result, African American men exhibit the highest incidence and mortality of PCa even when adjusted for socioeconomic factors such as access to health care. Thus, biological factors must be causing these health disparities at some level, but these factors are not yet clearly understood. Certain molecular events in the genome are already known to be associated with more or less aggressive forms of PCa. These molecular events (genetic lesions, and epigenetic alterations, overexpression or underexpression of certain genes) could be targeted for diagnosis and treatment and should help stratify patients exhibiting different forms of PCa into therapy regimens most appropriate for them. To date, PCa tissues analyzed for such purposes, however, have been mostly drawn from men of European ancestry. Data generated by The Cancer Genome Atlas contains only 27 AAs (6% of total 413 patients), making it difficult to assess racial differences and limiting the success of new advances in treatment. For instance, in September 2013 the Food and Drug Administration approved a new PCa-specific urine test meant to improve the use of the prostate-specific antigen (PSA) blood test for detecting higher-risk patients and decrease overdiagnosis and overtreatment of PCa. The new test relies on detection of biomarkers specific to PCa in the urine, and it is a significant advancement in the management of PCa. Yet the test may exacerbate PCa health disparities since AA men have lower frequency of these biomarkers but exhibit more aggressive disease overall. Discoveries in European American (EA) men may lead to more precise, personalized, and targeted therapies generally, but AA men may require a different, more specific set of diagnostic tests. At the same time, lack of comprehensive genomics data in AA men may delay or even halt progress in overcoming PCa health disparities. This project will characterize both known (Aim 1) and novel (Aim 2) molecular events in a sample set of PCa tissues from AA men, which will contribute to larger efforts by PCa research community to identify new ways to manage the disease in AA men. We will utilize a large sample set PCa tissue collected from Roswell Park Cancer Institute and the North Carolina-Louisiana Prostate Cancer Project from both AA and EA men. The majority of these samples have been matched with benign tissues from the same patients. In the first part of the project, we will generate comprehensive genetic profiles of molecular lesions previously known to be clinically relevant in PCa. This will allow us to assess differences in frequency of these lesions between racial groups. In the second part of the project, we will utilize high-resolution and highly sensitive technologies to detect as yet unknown genetic and epigenetic events in PCa in AA men, even if they are of very low frequency. These findings will point to new biomarkers specific to PCa in AA patients, which should ultimately lead to new tools for detection of high-grade PCa and provide new paths for AA men to enter into treatment regimens specifically appropriate to them. Upon completion of this project, new molecular diagnostic and prognostic tests for AA patients could foreseeably be developed within a matter of a few short years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710115
Entities
People
- Anna Woloszynska-read
Organizations
- United States Army