Evaluation of Multiple Risk–Associated Single Nucleotide Polymorphisms Versus Prostate-Specific Antigen at Baseline to Predict Prostate Cancer in Unscreened Men

BACKGROUND: Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear. OBJECTIVE: Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men. DESIGN, SETTING, AND PARTICIPANTS: This study used a nested case-control design based on the Malmö Diet and Cancer cohort with 943 men diagnosed with prostate cancer and 2829 matched controls. Blood samples were collected between 1991 and 1996, and follow-up lasted through 2005. MEASUREMENTS: We genotyped 50 SNPs, analyzed prostate-specific antigen (PSA) in blood from baseline, and tested for association with prostate cancer using the Cochran-Mantel-Haenszel test. We further developed a predictive model using SNPs nominally significant in univariate analysis and determined its accuracy to predict prostate cancer. RESULTS AND LIMITATIONS: Eighteen SNPs at 10 independent loci were associated with prostate cancer. Four independent SNPs at four independent loci remained significant after multiple test correction (p