Genetic variants in microRNAs and microRNA target sites predict biochemical recurrence after radical prostatectomy in localized prostate cancer

Abstract

Recent evidence indicates that microRNAs might participate in prostate cancer initiation, progression and treatment response. Germline variations in microRNAs might alter target gene expression and modify the efficacy of prostate cancer therapy. To determine whether genetic variants in microRNAs and microRNA target sites are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We retrospectively studied two independent cohorts composed of 320 Asian and 526 Caucasian men with pathologically organ-confined prostate cancer who had a median follow-up of 54.7 and 88.8 months after RP, respectively. Patients were systematically genotyped for 64 single-nucleotide polymorphisms (SNPs) in microRNAs and microRNA target sites, and their prognostic significance on BCR was assessed by Kaplan-Meier analysis and Cox regression model. After adjusting for known clinicopathologic risk factors, two SNPs (MIR605 rs2043556 and CDON rs3737336) remained associated with BCR. The numbers of risk alleles showed a cumulative effect on BCR [perallele hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.16-2.21, p for trend = 0.005] in Asian cohort, and the risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15-2.08, p for trend = 0.004) and in combined analysis (HR 1.57, 95% CI 1.26-1.96, p for trend <0.001). Results warrant replication in larger cohorts. This is the first study demonstrating that SNPs in microRNAs and microRNA target sites can be predictive biomarkers for BCR after RP.

Keywords: biochemical recurrence; microRNA; prostate cancer; radical prostatectomy; single-nucleotide polymorphism.