rs1512268

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).

Genome-wide association study of 474 prostate cancer cases and 458 controls from West African men identified a novel prostate cancer susceptibility locus at 10p14 marked by rs7918885 (p=1.29×10⁻⁷), localized to an intron of the lncRNA gene RP11-543F8.2. A stratified analysis by Gleason score revealed additional associations including rs34575154 in PCDHA1 at 5q31.3 (p=3.66×10⁻⁸) for high-grade disease and rs985081 at Xq28 (p=8.66×10⁻⁹) for low-grade disease. Validation in the African Ancestry Prostate Cancer GWAS Consortium showed limited replication, with only rs2993385 at 10p14 reaching nominal significance (p<0.05), highlighting population-specific genetic architecture.

Systematic literature review of 22 GWAS studies identifying 53 SNPs in 29 genomic loci associated with aggressive and progressive prostate cancer, particularly in low-grade disease. Functional analysis of 21 SNPs revealed involvement in the MYC/POU5F1B pathway (rs1447295, rs6983267, rs4242382), androgen receptor pathway (rs17021918, rs10486567, rs7679673, rs2939244), and PSA/KLK3 biomarkers (rs2735839, rs10993994). SNPs were integrated with somatic copy number aberration data, with 17 SNPs found in regions of recurrent CNAs predictive of progression; notably, rs1447295 and 7 other SNPs cluster in 8q24 gain regions harboring MYC.

This meta-analysis of genome-wide association studies identified 30 prostate cancer risk-associated SNPs in Caucasian populations. The SNPs had odds ratios ranging from 1.12-1.47, except rs16901979 (OR=1.80). These 30 SNPs collectively explained approximately 13.5% of the total genetic variance in prostate cancer risk, with individual SNPs explaining 0.2-0.9% of variance.

This systematic review identified 53 unique SNPs in 29 genomic loci associated with aggressive prostate cancer progression and poor outcomes from GWAS studies. Functional studies implicated 21 SNPs as modulating the androgen receptor pathway, MYC oncogene, and PSA-related genes, with rs1447295 and rs10993994 being replicated across multiple populations and associated with unfavorable pathological features in low-grade prostate cancer.