Association Of HEXO1 Gene Polymorphism With Hepatocellular Carcinoma And Its Clinical Characteristics

ObjectiveshEXO1 is the only exonuclease gene in MMR system, it plays an important role in the replication, repair, recombination and telomere stabilization process of the DNA, hEXO1 gene mutation and inactivation will promote tumor development and shorten the survival time of cancer patients. Studies in recent years show that, hEXO1 gene polymorphisms are associated with a variety of lung cancer, colorectal cancer, stomach cancer, breast cancer and cancer of the oral cavity. This study was designed to investigate hEXO1 single nucleotide polymorphisms (single nucleotide polymorphism, SNP) and HCC (hepatocellular carcinoma, HCC) association studies of genetic susceptibility and clinical features.MethodsSNPs that may affect expression or function of the gene were screened by using bioinformatics analysis firstly. By the United States Environmental Health Sciences (National Institute of Environmental Health Sciences, NTEHS) database, Chinese population hEXO1 gene minor allele frequency (minor allele frequency, MAF) is greater than 0.05 hypermutation sites screened hEXO1 three sites:rs1047840 (G> A), rs1776148 (G> A), rs3754093 (G> A) were selected.1199 patients without HCC were selected as a control group,1196 patients with HCC were selected as the case group. High flux TaqMan MGB real-time quantitative polymerase chain reaction (RT-PCR) technique was applied to genotyping for rs1047840, rs1776148, rs3754093 of hEXO1 gene. The binary unconditioned Logistic regression model was adopted to analyze the association between the rs1047840, rs1776148, rs3754093 single nucleotide polymorphisms (SNP) and the risk of HCC, as well as to evaluate the interaction between the SNPs and the environmental factors.Results(1) Basic information of the study subjects:The distributions of age, gender, nation in the cases and the controls has no statistical significance (P>0.05), equally comparable. However, the distributions of smoking, HBV infection and family history of HCC in the two groups are statistically significant (all P<0.05).(2) Hardy-Weinberg test results:Tested by HaploView4.2, in the controls, the genotype distributions of rsl047840,rsl776148, rs3754093 are in the HWE.(3) Distribution of genotype frequency:No statistical significance was found in the distributions of genotypes of rs1047840, rs1776148, rs3754093 Multiariable Logistic regression analysis showed that rs3754093 (AG) genotype might reduce risk of HCC.(4) Stratification analysis:The results of stratification analysis on HBV infection and family history of HCC indicated that SNP of rs3754093 is statistically associated with HCC occurrence. No statistical association was found between HCC and SNPs of rs1047840 and rsl776148.(5) Gene-environment interactions:Gene-environment interactions were found between rs1047840, rs1776148, rs3754O93 and environmental risk factors of smoking, drinking, HBV infection, and family history of HCC.(6) Gene-gene interaction:Gene-gene interaction existed between SNPs of rs1047840 and rs3754093, rsl776148 and rs3754093.(7) The association between SNPs of hEXO1 and clinic-pathological features in HCC:Chi-square test and multivariate logistic regression results showed that rs1047840, rs1776148, rs3754093 polymorphism and tumor size, tumor number, whether the nodule, liver cirrhosis, cancer embolus had no statistically significant differences.ConclusionMutation of rs3754093 might reduce the risk of HCC. The interactions between rs1047840, rs1776148, rs3754093 and environmental risk factors were associated with HCC occurrence.