Tan Shengkui, Qin Ruoyun, Zhu Xiaonian, Tan Chao, Song Jiale, Qin Linyuan, Liu Liu, Huang Xiong, Li Anhua, Qiu Xiaoqiang
Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, Guangxi, People's Republic of China.
Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
Oncotarget. 2016 Dec 27;7(52):87180-87193. doi: 10.18632/oncotarget.13517.
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.
人核酸外切酶1（hEXO1）是一种重要的核酸酶，参与错配修复系统，有助于维持基因组稳定性并调节DNA重组。本研究旨在探讨hEXO1单核苷酸多态性（SNP）与肝细胞癌（HCC）遗传易感性之间的关联。在中国广西开展的一项基于医院的病例对照研究中，对1196例病例（HCC患者）和1199例对照（非HCC患者）检测了hEXO1的SNP rs1047840、rs1776148、rs3754093、rs4149867、rs414996,3和rs1776181。我们发现rs3754093的AG基因型降低了HCC风险（OR=0.714，95%CI：0.539~0.946）。根据分层分析结果，rs3754093突变基因型AG/GG降低了HCC风险，这些风险降低与一些HCC保护因素有关，如不吸烟、不饮酒和无HCC家族史，但同时也降低了HBV感染患者的HCC风险。此外，它与无肿瘤转移相关，并提高了HCC患者的生存率。基因-环境相互作用分析结果表明，所有hEXO1 SNP在HCC发病机制中均与吸烟、饮酒、HBV感染相互作用。然而，基因-基因相互作用分析表明，rs3754093与其他5个SNP之间的相互作用与降低HCC风险有关。这些结果表明，rs3754093具有保护活性，可降低中国广西HCC的发病风险。此外，本研究中的所有SNP在HCC发病机制中均与环境风险因素相互作用。
