Genetic Variants in CASP3, BMP5, and IRS2 Genes May Influence Survival in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy

Several genome-wide association studies (GWAS) have been conducted to identify the common single nucleotide polymorphisms (SNPs) that influence the risk of prostate cancer. It was hypothesized that some prostate cancer-associated SNPs might relate to the clinical outcomes in patients treated for prostate cancer using androgen-deprivation therapy (ADT). A cohort of 601 patients who have received ADT for prostate cancer was genotyped for 29 SNPs that have been associated with prostate cancer in Cancer Genetic Markers of Susceptibility GWAS, and within the genes that have been implicated in cancer. Prognostic significance of these SNPs on the disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model. Three SNPs, namely CASP3 rs4862396, BMP5 rs3734444 and IRS2 rs7986346, were found to be closely associated with the ACM (P≤0.042), and BMP5 rs3734444 and IRS2 rs7986346 were also noted to be significantly related to the PCSM (P≤0.032) after adjusting for the known clinicopathologic predictors. Moreover, patients carrying a greater number of unfavorable genotypes at the loci of interest had a shorter time to ACM and PCSM during ADT (P for trend <0.001). Our results suggest that CASP3 rs4862396, BMP5 rs3734444 and IRS2 rs7986346 may affect the survival in patients after ADT for prostate cancer, and the analysis of these SNPs can help identify patients at higher risk of poor outcome.