rs12418451

A case-case association study of 18,343 prostate cancer patients (16,515 European, 1,828 African-American) evaluating 36 validated PC-risk SNPs found that rs2735839 (G allele) on chromosome 19q13 in the KLK3 gene was significantly and inversely associated with aggressive disease and high Gleason scores in both populations (p = 9.343 × 10⁻⁸ overall, p = 1.042 × 10⁻⁵ European, p = 2.0 × 10⁻⁴ African-American).

Comprehensive resequencing of a 122.9 kb region on chromosome 11q13.3 identified 644 polymorphic loci, including 166 novel variants not present in public databases. The study focused on fine-mapping prostate cancer susceptibility loci including rs10896438, rs12793759, rs10896449, and rs11228565, cataloguing 22-25 highly correlated surrogates (r² ≥ 0.8) for each locus and identifying functional regulatory elements. Indel polymorphisms comprised 13.4% of identified variants, with 58.5% novel to this study.

This case-case study of 5,895 prostate cancer patients from Johns Hopkins Hospital examined 20 genome-wide association study (GWAS)-identified risk SNPs for association with clinicopathologic variables of cancer aggressiveness. Only rs2735839 in KLK3 (p = 8.4 × 10⁻⁷) and rs10993994 in MSMB (p = 0.046) showed significant associations, but notably with the risk alleles being more frequent in less aggressive rather than more aggressive disease, likely reflecting PSA detection bias. The vast majority of the 20 tested SNPs showed no association with Gleason score, tumor stage, or aggressive disease phenotypes, suggesting they identify overall prostate cancer risk rather than aggressiveness.