rs266849

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 GWAS replication study evaluated 800 SNPs in African American (n=417) and European American (n=455) prostate cancer cases versus controls (n=925 AA, n=1,687 EA) from the NC-LA Prostate Cancer Project. Of 32 European-based GWAS SNPs, 13 were significant at P<0.05 in European Americans and 4 in African Americans (rs6983267, rs7017300, rs1859962, rs6501455). Two additional SNPs reached study-wide significance: rs1472606 (OR=1.43 in EA) and rs9351265 (OR=1.48 in AA). The study confirms a large proportion of cancer-associated regions from European GWAS but shows limited predictive value (AUC=0.60 in EA, 0.56 in AA) for clinical screening.

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.

This paper applies a bias correction method for odds ratio estimates from GWAS discovery data, demonstrating that the 'winner's curse' affects initial effect size estimates. The authors applied conditional maximum likelihood estimation to correct bias in GWAS findings from multiple complex diseases (breast cancer, colorectal cancer, lung cancer, prostate cancer, type I and II diabetes) and show that bias-adjusted odds ratios are substantially more consistent with subsequent replication studies, with selection-adjusted confidence intervals providing better uncertainty quantification than uncorrected estimates.