The study found pathogenic or likely pathogenic variants in DNA damage repair genes and HOXB13 to be more frequently observed in Black men with a family history of cancer.
“It’s our hope that these findings help Black men become more aware of their susceptibility to early-onset prostate cancer," said Kathleen Cooney, MD.
Germline variants in DNA damage repair (DDR) genes and HOXB13 that may be inherited may be important risk factors for Black men receiving a diagnosis of early-onset prostate cancer, according to recent findings from a study conducted by a team at Duke University, Durham, North Carolina.1
“We completed sequencing at Duke and our results reveal that men who had certain genetic variants were more likely to have a close relative diagnosed with cancer, have a higher prostate-specific antigen at time of diagnosis, and have more severe cases,” senior author Kathleen Cooney, MD, explained in a news release on the findings.2 Cooney is the George Barth Geller Distinguished Professor of Medicine and chair of medicine at Duke University.
To date, most genetic studies on prostate cancer susceptibility have largely recruited non-Hispanic White men, despite data showing Black men are more likely to develop prostate cancer and twice as more likely to die from the disease. Investigators in this recent study sought to address this health disparity by identifying genetic variants in Black patients who received a diagnosis of early-onset prostate cancer.
The study included 743 Black men receiving a diagnosis of early-onset prostate cancer at age 62 years or younger. Whole-exome sequencing of germline DNA was performed on DNA found in the men’s sperm cells. Analysis of the DNA focused on a panel of DDR genes and HOXB13. Discovered variants from the sequencing were ranked based on pathogenic potential taken from Rare Exome Variant Ensemble Learner score, evidence from existing literature, and prevalence in the cohort.
Investigators found 26 unique pathogenic or likely pathogenic (P/LP) variants in 14 genes (including HOXB13, BRCA1/2, BRIP1, ATM, CHEK2, and PALB2) among 4% of the patient population (30/743). They also found 33 unique variants of unknown significance in 16 genes among 39 patients. Since these genes are considered to be rare relative to their prevalence in the general population, the associations between the clinical characteristics were not found to be statistically significant.
The authors concluded that carriers of the discovered P/LP variants are more likely to have a first-degree relative with a history of DDR gene-associated cancer, have a higher prostate-specific antigen level at the time of diagnosis, and receive a diagnosis of metastatic disease.
“It’s our hope that these findings help Black men become more aware of their susceptibility to early-onset prostate cancer. If men know they have a family history of cancer, it’s important to talk to a doctor and consider genetic testing. If they end up having a mutation, they’re encouraged to have cancer screenings earlier and more frequently,” Cooney said in the news release.
1. Trendowski MR, Sample C, Baird T, et al. Germline variants in DNA damage repair genes and HOXB13 among Black patients with early-onset prostate cancer. JCO Precision Oncology. Published online November 29, 2022. Accessed on December 12, 2022. doi:10.1200/PO.22.00460
2. Family history, gene variants put Black men at risk for early prostate cancer. News release. Duke University. November 29, 2022. Accessed December 12, 2022. https://corporate.dukehealth.org/news/family-history-gene-variants-put-black-men-risk-early-prostate-cancer