A groundbreaking study has identified five rare gene variants strongly linked to aggressive and metastatic prostate cancer in men of African ancestry. Published in European Urology, the research marks a major step toward improving early detection and tackling long-standing disparities in prostate cancer outcomes among Black patients.
Scientists from the Center for Genetic Epidemiology at the Keck School of Medicine of USC led the largest study to date examining rare genetic variants tied to prostate cancer in this population. By analyzing genetic data from more than 12,000 Black men across North America and Africa including over 7,000 prostate cancer cases the researchers pinpointed five genes with unusually strong associations to severe disease: ATM, BRCA2, CHEK2, HOXB13, and PALB2.
According to the findings, men carrying harmful variants of these genes were up to six times more likely to develop prostate cancer than those without them. The team also demonstrated that combining genetic information from these five genes with a polygenic risk score and family medical history produces a more accurate and personalized prediction of prostate cancer risk.
Dr. Fei Chen, the study's first author, said the goal is to help identify the men most likely to face life-threatening forms of the disease. “We want to pinpoint those at high risk of developing aggressive or metastatic prostate cancer so they can work with their doctors to start screening earlier and monitor more closely,” Chen explained.
The study also highlights stark differences in disease patterns. While screening and treatment advances have improved survival rates, Black men continue to experience higher rates of aggressive prostate cancer and higher mortality than other groups. The newly identified gene markers offer a path toward narrowing this gap through more precise and timely screening.
The researchers evaluated how combining key genetic markers with the existing polygenic risk score a tool that incorporates 451 common genetic variants enhanced predictions across the study population. They found that men who carried dangerous gene variants, had a family history of prostate cancer, and ranked in the top 10% for polygenic risk faced dramatically higher odds: seven times more likely to develop prostate cancer, 18 times more likely to develop aggressive disease, and 34 times more likely to develop metastatic cancer.
Current guidelines recommend starting prostate cancer screening at age 45, or at 40 for Black men and those with a family history or known gene mutations. However, these risk factors are traditionally used separately. The new approach integrates all relevant genetic and family data to provide a more precise assessment helping doctors tailor screening schedules to individual risk.
Experts say such personalized risk estimation could reduce overdiagnosis and unnecessary biopsies in men with low-risk profiles, while ensuring high-risk patients receive the earliest possible intervention, when treatment is most effective.
“People at low risk may never develop prostate cancer or may develop a slow-growing type that poses little danger,” Chen said. “This approach allows them to avoid unnecessary stress and treatment. For those at high risk, it could be lifesaving.”
The study’s insights advance efforts to make prostate cancer screening more equitable, accurate, and effective and represent a promising step toward reducing racial disparities in one of the world’s most common cancers.