OBJECTIVETo use a hospital-based case-control study design to investigate the relationship between hepatocellular carcinoma (HCC) and the interaction of polymorphisms in the human mismatch repair gene,hMSH2,with environmental factors.

METHODSCases of new-onset,histopathology-diagnosed,and untreated (no chemotherapy or radiation therapy) HCC were enrolled between September 2009 and September 2012.A non-HCC healthy control group was also enrolled and was composed of individuals living in the same region as the cases for more than 10 years and age-/sex-matched with similar socioeconomic characteristics.All enrollees underwent hMSH2 genotyping by real-time PCR.T-test,chi-square test and unconditional logistic regression analysis was used to analyze the difference in allele frequencies among the case and control groups and the relationship between hMSH2 polymorphisms and environmental factors.

RESULTSFrequencies of hMSH2 rs2303428 CC,CT and TT genotypes in the HCC group were significantly different than in the control group (14.13% vs.8.21%,47.02% vs.49.47%,and 38.85% vs.42.32%;x 2=8.289,P =0.016).Individuals carrying the hMSH2 rs2303428 T allelic gene had a significantly increased risk compared to those with the hMSH2 rs2303428 C allelic gene (adjusted OR=1.228).Interactions were found between the hMSH2 genotype and hepatitis B surface antigen (HBsAg)-positive hepatitis infection (adjusted OR=1.865) and history of cancer (adjusted OR=5.634).There was no relation between hMSH2 gene rs4952887 and rs2059520 and liver cancer development or interaction with environmental factors.

CONCLUSIONThe hMSH2 rs2303428 genotype is positively related to risk of HCC in Chinese,with HBsAg-positive hepatitis infection starus and history of cancer increasing the risk.