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: Shengkui Tan, Ruoyun Qin, Xiaonian Zhu, Chao Tan, Jiale Song, Linyuan Qin, Liu Liu, Xiong Huang, Anhua Li, Xiaoqiang Qiu
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 52 Pg. 87180-87193 (Dec 27 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27894089 (Publication Type: Journal Article)

Chemical References

• EXO1 protein, human
• Exodeoxyribonucleases
• DNA Repair Enzymes

Topics

• Adult
• Carcinoma, Hepatocellular (etiology, genetics, pathology)
• DNA Repair Enzymes (genetics)
• Epistasis, Genetic
• Exodeoxyribonucleases (genetics)
• Female
• Gene-Environment Interaction
• Humans
• Liver Neoplasms (etiology, genetics, pathology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk