Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

Genetically adjusted PSA levels for prostate cancer screening.

Abstract

Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10-8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGSPSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P = 6.2 × 10-14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10-12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P = 7.2 × 10-4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View