Polymorphisms in miR-17-92 cluster promoter region is associated with risk and prognosis of endometrial cancer.

Abstract

Accumulating researches have reported that miR-17-92 cluster expression has strong association with tumorigenesis. In this study, we investigated the effects of 2 genetic polymorphisms in the promoter region of the miR-17-92 cluster and the risk and prognosis of endometrial cancer in northern Chinese women. Two polymorphisms (rs9588884 and rs982873) in the promoter of miR-17-92 cluster were genotyped by polymerase chain reaction and ligase detection reaction (PCR-LDR) in398 EC patients and 420 controls. The levels of miR-17-92 mRNA were investigated in 65EC tissues by real-time quantitative polymerase chain reaction (RT-qPCR). The impact of genetic features on the risk and clinical outcomes of EC was analyzed. The prognostic value of hsa-miR-17 and hsa-miR-20a in EC patients was assessed using the Kaplan-Meier plotter database. The results showed that a significant decrease in risk of EC with rs9588884 (GG vs CC: OR = 0.49, 95% CI = 0.32-0.78, P = .002; G vs C: OR = 0.75, 95% CI = 0.62-0.91, P = .005, respectively). Similarly, association was found between rs982873 and a decreased risk of EC (CC vs TT: OR = 0.53, 95% CI = 0.34-0.82, P = .004; C vs T: OR = 0.77, 95% CI = 0.63-0.94, P = .010, respectively). Moreover, survival analysis showed that the CG or GG genotype of rs9588884 may significantly increase overall survival (OS) compared with the CC genotype in the 5-year follow-up (HR = 0.49, 95% CI = 0.29-0.82 and HR = 0.36, 95% CI = 0.16-0.83, respectively). RT-qPCR results showed that the expression level of miR-17-92 mRNA in EC tissues with the rs9588884 GG genotype was significantly lower than those with the GC + CC genotype (P = .030). However, there was no significant difference in the prognosis and expression level of miR-17-92mRNA in tissues of EC patients with different genotypes of rs982873 (P = .343). In addition, analysis using Kaplan-Meier plotter database showed that high hsa-miR-20a expression was significantly correlated with poor OS in EC patients (HR = 1.63, 95% CI = 1.02-2.61, P = .039). The genetic polymorphisms rs9588884 and rs982873 in the promoter of miR-17-92 cluster decreased EC risk. Both rs9588884 and the expression level of hsa-miR-20a mRNA may be associated with its clinical outcome in EC patients.