rs10486567

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).

Developed a multi-state genetic variant-based Markov model for personalized prostate cancer risk stratification using Finnish population data. The model incorporates three primary SNPs (rs4242382 OR=1.75, rs138213197 OR=3.60, rs200331695 OR=6.0) and an extended panel of genetic variants to predict 10-year PCa risk ranging from 43% in the top 5% risk group to 11% in the bottom 60%, with recommendations for age-optimized screening (47 years for highest risk vs 55+ years for average/low risk) and risk-adapted interscreening intervals (< 1 year to 6+ years).

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.

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.

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.

Case-control study of 127 African American prostate cancer cases and 345 controls from the Flint Men's Health Study examining 24 SNPs previously associated with prostate cancer in European populations. Found nominal evidence (P<0.05) for association with three 8q24 SNPs (rs6983561 OR=1.55, rs16901979 OR=1.60, rs7000448 OR=1.41) and two 10q11 SNPs (rs7904463, rs10740051 OR=0.51), replicating 8q24 findings in African Americans and providing first evidence for MSMB region association in this population.

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 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.

A nested case-control study in two prospective cohorts (CPS-II and PLCO) examining whether HNF1B and JAZF1 variants associated with both diabetes and prostate cancer mediate the inverse relationship between these diseases. Three HNF1B SNPs (rs11649743, rs4430796, rs7501939) were associated with decreased prostate cancer risk (OR 0.84-0.86) and marginally increased diabetes risk, while two JAZF1 SNPs (rs6968704, rs10486567) were associated with decreased prostate cancer risk but not diabetes. The associations persisted after stratification by diabetic status, indicating that diabetes does not mediate the SNP-prostate cancer relationships.

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.

This Finnish family-based study analyzed gene-gene interactions between rs4242382 (8q24) and rs10486567 (7p15.2) in 947 subjects from 76 families with 228 prostate cancer cases. The risk allele A at rs4242382 showed OR=1.14 (95% CI 1.08-1.19) and rs10486567 showed OR=1.06 (95% CI 1.01-1.11) with a significant multiplicative gene-gene interaction (P<0.0001), suggesting synergistic epistasis for familial multiple prostate cancer, particularly in non-aggressive disease.