Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels.
Parikh H, Wang Z, Pettigrew KA, Jia J, Daugherty S, Yeager M, Jacobs KB, Hutchinson A, Burdett L, Cullen M, Qi L, Boland J, Collins I, Albert TJ, Vatten LJ, Hveem K, Njølstad I, Cancel-Tassin G, Cussenot O, Valeri A, Virtamo J, Thun MJ, Feigelson HS, Diver WR, Chatterjee N, Thomas G, Albanes D, Chanock SJ, Hunter DJ, Hoover R, Hayes RB, Berndt SI, Sampson J, Amundadottir L
Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56 kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case-control studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P = 0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P = 3.41 × 10(-4), per-allele trend odds ratio (OR) = 0.77, 95% CI = 0.67-0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score <7 and disease stage