Genetically adjusted PSA levels for prostate cancer screening.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 37264206.
- Also identified by DOI 10.1038/s41591-023-02277-9 and PMC identifier 10287565.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-8</sup>) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGS<sub>PSA</sub>) 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<sup>-14</sup>, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10<sup>-12</sup>, 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<sup>-4</sup>). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.
Medical subject headings
- Prostatic Neoplasms