Huge Prostate Cancer Genetics Study Highlights Disparities in Risk, Research

Data from 200,000 men gathered worldwide have helped reveal 86 new genetic variants that can boost the risk for prostate cancer, boosting by 46% the number of known risk factors in a study that shed new light on why men of African ancestry inherit about twice the prostate cancer risk as those of European descent.

The study, published this week in Nature Genetics, is the largest study of prostate cancer genetics and tries to address a vexing problem in the field: while prostate cancer risk is far higher and more deadly among Black men compared with White men, most studies are overenrolled with Whites, limiting the ability to understand and treat patients based on ethnic differences.

Investigators applied a model that assessed prostate cancer risk based on the relationship of various genetic factors, which showed that men with African ancestry inherit about twice the prostate cancer risk compared to those of European ancestry. Men with Asian ancestry inherit about three-quarter the risk of their white counterparts; this shows that genetics has some part in the likelihood of prostate cancer occurring in certain racial groups and can aid precision medicine models in early detection of prostate cancer.

"Our long-term objective is to develop a genetic risk score that can be used to determine a man's risk of developing prostate cancer," corresponding author Christopher Haiman, ScD, professor of preventive medicine at the USC Keck School of Medicine and director of the USC Center for Genetic Epidemiology, said in statement. "Men at higher risk may benefit from earlier and more frequent screening, so the disease can be identified when it's more treatable."

That’s important, because when to screen for prostate cancer has been something of a health care football over the past decade. Right now, US Preventive Services Task Force screening guidelines suggest that those 55 and older with average risk can take a prostate-specific antigen (PSA) test. Although high PSA levels are associated with prostate cancer, use of the test after a 2012 USPSTF pulled back on its recommendation, because it felt there was too much unnecessary treatment.

A more value-based approach to the PSA test would use it selectively to monitor those known to be at high-risk for prostate cancer. That’s where a genetic risk score would help, as these men would start PSA screening at much younger ages. Such an approach would need to be tested in a clinical trial, Haiman said.

"Most important, unlike previous screening trials, this one would need to be more representative of the diversity we see in the world," he said. "No population should get left behind."

Reference

Conti, D.V., Darst, B.F., Moss, L.C. et al. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet 2021;53:65–75 https://doi.org/10.1038/s41588-020-00748-0