rs2569735

Fine mapping study of the KLK3 locus (chromosome 19q13.33) in 3,522 prostate cancer cases and 3,338 controls identified three highly correlated SNPs (rs17632542, rs62113212, rs62113214) associated with nonaggressive prostate cancer (P = 4.72×10⁻⁵ to 5.74×10⁻⁵, OR = 0.68-0.69 per allele). The previously reported marker rs2735839 showed no significant association (P = 0.20). Baseline PSA levels were 43.7% lower in carriers of minor alleles at the three SNPs (P = 9.70×10⁻⁵), suggesting germline KLK3 variants influence PSA screening-detected prostate cancer.

Genome-wide association study identifying rs17632542 (Ile179Thr) in KLK3 gene as a strong prostate cancer susceptibility variant (combined P = 1.9 × 10⁻³⁴, OR = 0.66) across 10,405 cases and 10,681 controls. The variant was also associated with PSA levels and molecular dynamics modeling suggested it could alter protein stability or affect RNA splicing of KLK3.

A comprehensive resequencing analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33 in 78 individuals of European ancestry using 454 next-generation sequencing. The authors identified 555 polymorphic loci including 116 novel SNPs and 182 novel insertion/deletion polymorphisms. They discovered 11 coding variants in KLK3 (5 non-synonymous, 1 frameshift), 4 in KLK15, and 5 in KLK2. The key SNP rs2735839 lies in a region of relatively low linkage disequilibrium; two markers (rs2569735, rs1058205) in high LD (r²≥0.8) with rs2735839 were identified. This catalog of common genetic variation provides a foundation for fine-mapping studies of prostate cancer susceptibility and PSA regulation.