Five key genes have been linked with aggressive or metastatic prostate cancer in men of African descent, according to the largest study to date in this population.
Men carrying disease-causing variants in these predisposition genes were up to six times more likely to develop prostate cancer than others, with risk varying widely among the thousands of individuals studied.
However, it could be more precisely gauged using information on germline pathogenic variants from predisposing genes, family history and a polygenic risk score.
The research, in European Urology, suggests that stratified cancer screening programs could therefore help to identify high-risk individuals who might benefit from screening at an earlier age.
On an individual level, the findings could lead to more personalized risk assessment for prostate cancer among these patients and aid decisions on screening and treatment.
“Our goal is to better understand risk and help reduce the disparity in prostate cancer outcomes,” explained lead researcher Fei Chen, PhD, from the University of Southern California.
“We want to identify people who are at high risk of developing aggressive or metastatic prostate cancer. Those patients could then work with their doctors to make decisions about starting screening sooner and testing more frequently in hopes of finding the disease in its early stages.”
Black men are more likely to develop aggressive forms of prostate cancer and die from it than others.
Chen and team compared 37 prostate cancer predisposition genes in 7176 men with African ancestry who had prostate cancer with 4873 who did not have the cancer from seven countries across North America and Africa.
Germline pathogenic variants in the following genes were linked with aggressive or metastatic prostate cancer: ATM, BRCA2, CHEK2, HOXB13, and PALB2.
These variants presented in four percent of cases with these forms of the cancer and they were significantly associated with aggressive prostate cancer, with odds ratios ranging from 2.18 to 5.96.
The authors noted that a man’s absolute, lifetime absolute risk varied widely depending on whether they carried a pathogenic variant or had a family history.
Risk ranged from 3.0% to 74% for prostate cancer overall, from 0.6% to 41% for aggressive prostate cancer, and from 0.2% to 37% for metastatic prostate cancer.
People who carried variants of prostate cancer predisposition genes had a positive family history and also a polygenic risk score in the top 10% had a risk of overall, aggressive and metastatic prostate cancer that was respectively seven, 18, and 34 times that of average-risk individuals.
“This study adds to the growing evidence in favor of risk-tailored cancer screening strategies, advocating for earlier and more frequent screening for high-risk individuals, and delayed and less frequent screening for those at lower risk, to improve early detection of aggressive [prostate cancer] while minimizing overdiagnosis,” the researchers reported.
They added: “Importantly, the ability to more accurately assess an individual’s risk of developing aggressive disease, particularly in African ancestry populations, may inform screening guidelines that prioritize personalized risk over race-based recommendations.”
