Research Papers:

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

Shengkui Tan, Ruoyun Qin, Xiaonian Zhu, Chao Tan, Jiale Song, Linyuan Qin, Liu Liu, Xiong Huang, Anhua Li and Xiaoqiang Qiu _

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Oncotarget. 2016; 7:87180-87193. https://doi.org/10.18632/oncotarget.13517

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Shengkui Tan1, Ruoyun Qin2, Xiaonian Zhu1, Chao Tan3, Jiale Song1, Linyuan Qin1, Liu Liu2, Xiong Huang2, Anhua Li3, Xiaoqiang Qiu2

1Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, Guangxi, People’s Republic of China

2Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China

3Guangxi Center for Disease Prevention and Control, Nanning 530021, Guangxi, People’s Republic of China

Correspondence to:

Xiaoqiang Qiu, email: [email protected]

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


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.

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