Characterizing the Genetic Landscape of Prostate Cancer in Young African American Men
Abstract
African American men have a very high incidence of prostate cancer and also suffer from excess mortality compared to other racial/ethnic populations. Many factors may contribute to this problem including different access to health care and treatment choices as well as socioeconomic factors in general. There is also data to suggest that underlying biological differences exist that contribute to this disparity, and our proposal focuses specifically on inherited genetic variation as an explanation. There has been an increase in our knowledge about prostate cancer susceptibility genes. In addition to mutations in HOXB13, there is evidence implicating mutations in DNA repair genes in prostate cancer risk. We propose to use next-generation sequencing technologies to screen 750 African American men diagnosed with prostate cancer at a young age (before age 60 years) for mutations in a panel of 100 cancer genes. We are focusing on early-onset prostate cancer cases since these patients are more likely to have a genetic cause and less likely to have an environmental cause for their cancer. To identify the sample for testing, we are collaborating with Dr. Jennifer Beebe-Dimmer, a cancer epidemiologist and co-investigator at the National Cancer Institute-sponsored Detroit SEER (Surveillance, Epidemiology and End Results) program, which serves a racially diverse population. The Epidemiology Research Core (ERC) at Karmanos Cancer Institute will assist us in identifying the potential participants, collecting survey information, and obtaining a sputum sample for DNA. The DNA will be prepared at the University of Michigan where the sequencing will be performed. We will tabulate all of the mutations identified and compare them to publically available data from other largely non-African populations. We expect to identify ~40 men who harbor a known deleterious prostate cancer gene alteration. For these men, we will work with the ERC to go back and collect the tumor samples from these men for molecular analysis. We suspect that men with mutations in the same gene will have a similar molecular profile in their tumors. This is the first comprehensive analysis of germline variation in young African American men with clinically significant prostate cancer. The information generated from this research will be critically important for understanding why prostate cancer occurs in this high-risk population. There will be rapid translation to the clinical setting. Since we are looking for germline mutations, which are present from birth, men harboring germline mutations would be good candidates for early detection (for example, with scheduled PSA [prostate-specific antigen] tests and pelvic MRI [magnetic resonance imaging] at a young age) and prevention strategies (e.g., exercise, low-fat diets, and careful control of comorbid conditions).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610713
Entities
People
- Kathleen A. Cooney
Organizations
- United States Army
- University of Utah