rs1571801

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).

Case-only study of 603 prostate cancer cases examining gene-environment interactions between ALAD tagSNPs and occupational lead exposure. Two ALAD intron 1 SNPs (rs818684 and rs818689) showed significant interactions with high lead exposure in black cases (IOR 2.73, P=0.002 and IOR 2.20, P=0.017 respectively). rs2761016 showed interaction with low lead exposure in black cases (IOR 2.08, P=0.019). The rs818684 variant allele was associated with higher Gleason grade in both black (OR 3.96) and white (OR 2.95) cases with high lead exposure.

Analysis of 20 GWAS-identified prostate cancer susceptibility SNPs in 601 patients treated with androgen-deprivation therapy (ADT) found that rs16901979 at 8q24 was significantly associated with prostate cancer-specific mortality (HR = 0.63, 95% CI 0.45-0.87, p = 0.005) and rs7931342 at 11q13 was associated with mortality (HR = 0.65, 95% CI 0.43-0.98, p = 0.038). These variants may help predict survival outcomes in prostate cancer patients undergoing ADT treatment.

This study demonstrates that 13 of 14 previously identified prostate cancer risk SNPs are significantly associated with early-onset prostate cancer (EO PCa; diagnosed ≤55 years), with effect sizes ranging from OR=1.15 to OR=1.55 per risk allele. Early-onset cases carried significantly more cumulative risk alleles (mean 12.4) compared to older-onset CGEMS cases (mean 11.9; p=1.7×10⁻⁵), suggesting common genetic variants play an increased role in earlier disease manifestation.

This population-based case-control study evaluated 17 prostate cancer susceptibility loci identified in European GWAS populations in Chinese men (288 cases, 155 controls from Shanghai). Two of 17 loci on chromosome 8q24 showed significant associations with prostate cancer risk (rs1016343: OR=2.07, P=9.4×10⁻⁴; rs10090154: OR=2.07, P=0.002). Multiple additional SNPs at 8q24 regions 1 and 2 were also significantly associated with prostate cancer risk, while region 3 SNPs showed mostly null associations. Results suggest that prostate cancer risk variants identified in European populations are also relevant for Chinese men.

This methods paper presents a novel retrospective likelihood approach for estimating genotype relative risks from ascertained pedigrees, which adjusts for ascertainment bias by conditioning on the phenotypes of all pedigree members. The authors apply this method to 28 previously reported prostate cancer SNPs in Mayo Clinic pedigree data (469 affected men) and case-control samples (661 cases, 518 controls), demonstrating that relative risk estimates from pedigrees are consistent with odds ratios from case-control studies.

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 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.

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.