Genetically Adjusted PSA Levels Improve Prediction of Prostate Cancer

WEDNESDAY, June 7, 2023 (HealthDay News) -- Accounting for genetic determinants of constitutive, noncancer-related prostate-specific antigen (PSA) variation improves prediction of prostate cancer, according to a study published online June 1 in Nature Medicine.

Linda Kachuri, Ph.D., M.P.H., from the University of California in San Francisco, and colleagues conducted a multiancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGS_PSA) to account for constitutive PSA variation.

The researchers identified 128 genome-wide significant associations, and the resulting score accounted for 9.61 percent of constitutive PSA variation. In men of European ancestry, using PGS-adjusted PSA would avert up to 31 percent of negative prostate biopsies but also result in 12 percent fewer biopsies among patients with prostate cancer, mainly tumors with a Gleason score <7. Compared with unadjusted PSA, genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio, 3.44 versus 3.31; area under the curve, 0.755 versus 0.738). Including genetically adjusted PSA improved detection of aggressive disease compared with a prostate cancer PGS alone (area under the curve, 0.786 versus 0.712).

"We adjusted each person's PSA values based on his unique genetic profile," Kachuri said in a statement. "PSA values personalized in this way are more likely to reveal changes in PSA due to prostate cancer because they are corrected for the influence of inherited genetics."

Two authors disclosed ties to the biotechnology industry.

Abstract/Full Text