title: Associations between single-nucleotide polymorphisms of human exonuclease 1 and the risk of hepatocellular carcinoma.
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.
authors.affiliation: Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, Guangxi, People's Republic of China.
authors.forename: Shengkui
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Ruoyun
authors.initials: R
authors.lastname: Qin
authors.affiliation: Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, Guangxi, People's Republic of China.
authors.forename: Xiaonian
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Guangxi Center for Disease Prevention and Control, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, Guangxi, People's Republic of China.
authors.forename: Jiale
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, Guangxi, People's Republic of China.
authors.forename: Linyuan
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Guangxi Center for Disease Prevention and Control, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Anhua
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D045643:DNA Repair Enzymes / Q000235:genetics*; D004843:Epistasis, Genetic; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes
keywords: hepatocellular carcinoma (HCC); human exonuclease 1 (hEXO1); interaction; single-nucleotide polymorphisms (SNPs)