rs138213197

This genome-wide association study of 2511 familial prostate cancer cases and 1382 controls identified significant associations in six regions previously linked to prostate cancer risk. Most notably, rs138042437 at 8q24.21 achieved an exceptionally large effect size (OR=13.3, p=1.7e-8) and demonstrated strong co-segregation with disease in 116 affected relatives (p=8.5e-11). The study identified a rare segregating haplotype at 8q24.21 containing three SNPs (rs183373024, rs188140481, rs138042437) that characterized a prostate cancer predisposition locus.

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.

The study identified a novel rare germline mutation G135E in the HOXB13 gene significantly associated with prostate cancer risk in Chinese men (P=0.027). Three heterozygous carriers were found in 671 prostate cancer patients compared to zero in 1,536 controls, with evidence of a founder mutation effect. This finding, along with the previously identified G84E mutation in Caucasians, suggests rare mutations in HOXB13 play an important role in prostate cancer etiology.

Population-based case-control study of 1,310 prostate cancer cases and 1,259 controls found that the HOXB13 G84E mutation (rs138213197) was significantly associated with increased prostate cancer risk (OR=3.30, 95% CI 1.21-8.96), being present in 1.3% of cases versus 0.4% of controls. Results suggest potential associations with more aggressive disease features, though stratified analyses were limited by small mutation carrier numbers.