• Department of Urology, University of Texas Health Science Center San Antonio, San Antonio, Texas.
• State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
• Departments of Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
• Department of Urology, UC San Diego Health System, San Diego, California.

BACKGROUND: To investigate the ability of the prostate genetic score (PGS-33), a germ-line biomarker of prostate cancer (PCa) risk, to categorize men participating in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

METHODS: We obtained the genetic data from the Cancer Genetic Markers of Susceptibility (CGEMS), a nested case control study examining germ-line DNA in the screened arm of the PLCO trial. A PGS-33 was calculated based on their genotype at 33 PCa associated single nucleotide polymorphisms (SNPs). The primary outcome was the diagnosis of PCa and primary predictor was PGS-33.

RESULTS: We identified 2,244 subjects (no cancer, N = 1017) and cases (N = 1227). The PGS-33 (P<0.001), prostate specific antigen (PSA; P < 0.001), family history of PCa (< 0.001), abnormal digital rectal exam (DRE, P < 0.001), and history of ever smoking (P = 0.037) were associated with a PCa diagnosis. In multivariable analysis, the log (PGS-33) was associated with PCa diagnosis with an odds ratio of 1.68 (95% CI 1.36-2.08, P < 0.001), log (PSA) (OR 8.2; 95% CI 6.75-10.04, P < 0.001), and family history of PCa (OR 2.01; 95% CI 1.26-3.20, P = 0.003). PGS-33 quartiles noted an increasing rate of PCa detection in addition to PSA: 43.2% (Q1), 47.8% (Q2), 58.8% (Q3), and 69.4 (Q4) (P < 0.001) and improvement in PSA performance (P < 0.001).

CONCLUSIONS: Germ-line DNA in the form of the PGS-33 is able to risk stratify men regarding their risk of PCa. The PGS-33 may have implications regarding who may benefit most from PCa screening and possibly add to PSA performance.