The accuracy of prostate-specific antigen (PSA) screening can be improved by accounting for genetic factors that cause changes in PSA levels that are not associated with cancer, according to a multi-center study led by UC San Francisco and Stanford University.
In a study published on June 1, 2023 in Nature Medicine, UCSF researchers and their collaborators conducted a large genome-wide association study of PSA in more than 95,000 men without diagnosed prostate cancer, which identified over 80 novel PSA-associated variations. They set out to discover whether accounting for genetic factors that cause variations in the levels of PSA but are not attributable to cancer could help improve PSA screening.
“PSA levels represent the main diagnostic biomarker for prostate cancer. This test is widely used but not currently implemented as part of a formal screening program,” said Linda Kachuri PhD, MPH, a former postdoctoral scholar in the Department of Epidemiology & Biostatistics at UCSF and lead author of the study. “Because of its poor sensitivity and specificity, PSA testing can often lead to detecting latent disease or, in some cases, missing aggressive tumors.”
The researchers leveraged these new data to build a genome-wide polygenic score for PSA, measuring an individual’s genetic predisposition based on genetic variations.
“The polygenic score captured each individual’s genetic predisposition to high PSA levels,” said Rebecca Graff, ScD, UCSF assistant professor in the Department of Epidemiology & Biostatistics and one of the senior authors of the study. “The polygenic score was strongly associated with PSA levels in validation cohorts and was not associated with prostate cancer, confirming that it reflects benign PSA variation.”