Recent research led by the Center for Genetic Epidemiology at the Keck School of Medicine of USC has identified genetic variants linked to aggressive prostate cancer in individuals of African descent. The study, published in the journal European Urology, analyzed data from over 12,000 Black men and discovered variants in five key genes associated with aggressive forms of the disease, including those that metastasize to other organs.
The team’s findings highlight the disparities in prostate cancer outcomes for Black patients, who are disproportionately affected by aggressive disease and related mortality. By integrating genetic data with other risk assessment methods, the researchers aim to refine screening and treatment strategies for this population.
Identification of Key Genetic Variants
The study identified variants in the genes ATM, BRCA2, CHEK2, HOXB13, and PALB2. Participants carrying these variants exhibited a sixfold increase in the likelihood of developing prostate cancer compared to those without them. The research included more than 7,000 prostate cancer cases and nearly 5,000 control samples, making it the most extensive study to date focused on rare genetic variants related to prostate cancer in Black men.
Dr. Fei Chen, the study’s first author, emphasized the importance of this research, stating, “Our goal is to better understand risk and help reduce the disparity in prostate cancer outcomes.” The study aims to identify individuals at high risk for aggressive forms of the disease, enabling them to collaborate with healthcare providers on earlier and more frequent screening.
Advancing Personalized Risk Assessment
The researchers employed a polygenic risk score method, previously developed by Dr. Christopher Haiman, which calculates cancer risk based on the presence of 451 common gene variants. This approach, when combined with family history and specific gene variants, offers a more precise risk estimation for developing prostate cancer, particularly the aggressive forms.
The findings revealed a wide range of risk among study participants. Those with dangerous genetic variants, a family history of prostate cancer, and top-tier polygenic risk scores were found to be seven times more likely to develop the disease, 18 times more likely to have aggressive cancer, and 34 times more likely to experience metastatic cancer compared to individuals at average risk.
Dr. Chen noted, “The variability in risk in our study population supports the potential of using a more accurate estimate to develop personalized screening strategies.”
The study’s results could significantly impact screening recommendations, as the current guidelines from the National Comprehensive Cancer Network suggest beginning screening at age 45 for most individuals. For high-risk groups, including Black men and those with a family history of prostate cancer, screening may start as early as age 40.
Dr. Chen explained that combining information currently assessed separately can generate a more accurate risk estimate. This tailored approach could facilitate early detection of prostate cancer when treatment is most effective, while potentially reducing unnecessary biopsies and overtreatment of slow-growing tumors.
The ongoing research aims to further understand genetic links to prostate cancer among Black patients, with the polygenic risk score already being tested in clinical trials. Future studies may validate the inclusion of family history and genetic variants in risk estimates, potentially transforming prostate cancer screening and treatment for at-risk populations.