Associations between single-nucleotide polymorphisms of human exonuclease 1 and the risk of hepatocellular carcinoma

// Shengkui Tan 1 , Ruoyun Qin 2 , Xiaonian Zhu 1 , Chao Tan 3 , Jiale Song 1 , Linyuan Qin 1 , Liu Liu 2 , Xiong Huang 2 , Anhua Li 3 , Xiaoqiang Qiu 2 1 Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, Guangxi, People’s Republic of China 2 Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China 3 Guangxi Center for Disease Prevention and Control, Nanning 530021, Guangxi, People’s Republic of China Correspondence to: Xiaoqiang Qiu, email: xqqiu9999@sina.com Keywords: hepatocellular carcinoma (HCC), human exonuclease 1 ( hEXO1 ), single-nucleotide polymorphisms (SNPs), interaction Received: May 31, 2016 Accepted: October 17, 2016 Published: November 23, 2016 ABSTRACT Human exonuclease 1 ( hEXO1 ) is an important nuclease involved in mismatch repair system that contributes to maintain genomic stability and modulate DNA recombination. This study is aimed to explore the associations between single-nucleotide polymorphisms (SNPs) of hEXO1 and the hereditary susceptibility of hepatocellular carcinoma (HCC). SNPs rs1047840, rs1776148, rs3754093, rs4149867, rs4149963, and rs1776181 of hEXO1 were examined from a hospital-based case-control study including 1,196 cases (HCC patients) and 1,199 controls (non-HCC patients) in Guangxi, China. We found the rs3754093 AG genotype decreased the risk of HCC (OR=0.714, 95% CI: 0.539~0.946). According to the results of stratification analysis, rs3754093 mutant genotype AG/GG decreased the risk of HCC with some HCC protective factors such as non-smoking, non-alcohol consumption and non-HCC family history, but also decreased the risk of HCC with HBV infection. Moreover, it was correlated to non-tumor metastasis and increased the survival of HCC patients. The results from gene-environment interaction assay indicated all hEXO1 SNPs interacted with smoking, alcohol consumption, HBV infection in pathogenesis of HCC. However, gene-gene interaction assay suggested the interaction between rs3754093 and other 5 SNPs were associated with reducing the HCC risk. These results suggest rs3754093 exhibits a protective activity to decrease the incidence risk of HCC in Guangxi, China. In addition, all SNPs in this study interacted with environment risk factors in pathogenesis of HCC.