title: Prostate genetic score (PGS-33) is independently associated with risk of prostate cancer in the PLCO trial.
abstract: 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.
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Liss
authors.affiliation: 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.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Departments of Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Haitao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Urology, UC San Diego Health System, San Diego, California.
authors.forename: A Karim
authors.initials: AK
authors.lastname: Kader
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: PSA; genetics; prostate Cancer; screening