Researchers at the Wayne State University School of Medicine and the Barbara Ann Karmanos Cancer Institute have found inherited genetic variants mostly involved in the body’s response to acquired DNA damage that may be responsible for early-onset prostate cancer among some Black men.
Jennifer Beebe-Dimmer, Ph.D., M.P.H., professor of Oncology at WSU, leader of the Population Studies and Disparities Research Program and scientific director of the Epidemiology Research Core at Karmanos, led the WSU and Karmanos team in the study titled, “Germline Variants in DNA Damage Repair Genes and HOXB13 among Black Patients with Early-Onset Prostate Cancer,” recently published in the American Society of Clinical Oncology’s JCO Precision Oncology.
“The objective of this study was to examine the prevalence and spectrum of known mutations in cancer susceptibility genes in primarily DNA damage response pathways in African American men diagnosed with early onset prostate cancer,” Dr. Beebe-Dimmer explained. “Our knowledge about the importance of these genes in Black men with prostate cancer lags far behind our knowledge in men of European descent.”
One of the risk factors for prostate cancer is a family history of the disease, particularly when there is a father, brother or son who is diagnosed before age 65. These men are usually encouraged to speak with their doctor before the age of 50 to talk about their risk. However, if they are Black, they should speak with their doctor at age 45. Black men are more likely to be diagnosed with prostate cancer and die from the disease than their non-Hispanic White male counterparts, who are usually the subjects of most prostate cancer research.
“In the absence of genetic information, a family history of prostate cancer, particularly among close relatives — fathers, brothers and sons — is often used as a proxy measure of inherited genetic predisposition. There is a similar logic in looking at men with earlier onset disease. The thought is that these men have an inherited predisposition to disease, which is why it manifests at an earlier age,” Dr. Beebe-Dimmer said.
The team examined the DNA of more than 700 Black men 62 and younger who had been diagnosed with early-onset prostate cancer. From the gene sequence, they found about 4 percent of the men had HOXB13 (a gene first discovered in White men with hereditary prostate cancer) and decided to take a closer look.
The team hopes the findings on the genetic variants among Black men will help reduce the number of early-onset prostate cancer diagnoses and deaths from the disease. With this, they hope men who know they have a family history of prostate cancer will also consider genetic testing and talk to their doctors about prostate cancer screening.
“Mutations in the genes identified in this study not only help us to understand the underlying biology of prostate cancer in African American men, but our new knowledge of these mutations may also be used in the development and use of targeted treatments, as well as screening for earlier detection of disease in unaffected family members,” Dr. Beebe-Dimmer said.
For four years, Dr. Beebe-Dimmer has been working on this research with a group of WSU School of Medicine and Karmanos Cancer Institute researchers, including Matthew Trendowski, Ph.D., WSU medical student; Tara Baird, manager of the ERC, Karmanos and WSU; and Julie Ruterbusch, M.P.H, co-director of the ERC, member of the PSDR Program at Karmanos and WSU research assistant. The research was conducted in collaboration with Duke University, that team led by the senior author Kathleen Cooney, M.D.
The Department of Defense and the National Institutes of Health funded the study.
Read the study here.