Analysis of association of potentially functional genetic variants within genes encoding miR-34b/c, miR-378 and miR-143/145 with prostate cancer in Serbian population

Abstract

MiRNA-associated genetic variants occurring in regulatory regions can affect the efficiency of transcription and potentially modify pri-miRNA or pre-miRNA processing. Since miRNA-based mechanisms are shown to be involved in the pathogenesis of prostate cancer (PCa), the aim of the present study was to evaluate the effect of rs4938723, rs1076064 and rs4705343 occurring in regulatory regions of miR-34b/c, miR-143/145 and miR-378, respectively, on PCa risk and progression in Serbian population. We examined a total of 1060 subjects, of which 350 were patients with PCa, 354 were patients with benign prostatic hyperplasia (BPH), while 356 healthy volunteers were included in the control group. Genotyping of rs4938723, rs1076064 and rs4705343 was performed by using Taqman® SNP Genotyping Assays. Allele C of rs4705342 was found to increase the risk of PCa (P=0.031 for codominant model, P=0.0088 for recessive model). Rs1076064 minor allele G was found to associate with serum PSA score, as well as with PCa T category and disease aggressiveness. For rs4938723 minor allele C was shown to be associated with the lower PCa T category (Pdom=0.0046; OR=0.36, 95 % CI 0.17-0.76) in T2 vs. T1 comparison. Rs4705342 was identified as PCa susceptibility variant in Serbian population, while for rs1076064 and rs4938723 association with PCa progression parameters was found.