The Association Between hMLH1 and hMSH2 Polymorphisms and Renal Tumors in Northeastern China

Although hMLH1 and hMSH2 are closely associated with the development and drug resistance of multiple types of tumors, their role in renal tumors remains unclear. This study was designed to examine the relationship between renal tumor development and polymorphisms in the hMLH1 and hMSH2 genes. The study included 180 patients with renal tumors that were confirmed by pathological examination and 199 healthy controls. The clinical and pathological stages of the tumor samples were determined, and DNA was extracted from the peripheral blood of the subjects. Polymorphisms in the hMLH1 and hMSH2 loci were identified using the 1000 genomes database and the multiplex ligase detection method. Correlation analyses was performed using single nucleotide polymorphism tests. 88.9% (160/180) of the tumor specimens were identified as clear cell renal cell carcinoma (CCRC) and 89.4% (161/180) were stage I carcinomas. Three hMLH1 and nine hMSH2 polymorphic sites were identified, and the frequency of the AA genotype of the hMSH2 rs2303424 variant was found to be significantly higher in the renal tumor group (odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.02-1.86) in the additive model (p = 0.029), the recessive model (p = 0.005), and codominant model (p = 0.02). Multiple testing corrections were performed and the differences between the clear cell carcinoma and control samples remained significant. Compared with the controls, the distribution of the GG genotype of the hMSH2 rs11886591 locus was significantly higher in the clear cell carcinoma group (OR = 0.80, 95% CI: 0.59-1.10, p = 0.04) after multiple testing corrections in the dominant model. The AA genotype at the rs2303424 locus and GG genotype at rs11886591 locus of the DNA repair gene hMSH2 were closely associated with the development of renal tumors. Further studies are needed on larger cohorts to confirm this correlation.