XRCC4与XPC编码区突变与肝细胞癌的关联性研究

Correlation of mutations at coding regions of XRCC4 and XPC with hepatocellular carcinoma

目的探讨DNA修复基因XRCC4和XPC编码区突变对黄曲霉毒素B1(AFB1)相关性肝细胞癌(HCC)发病与预后的影响。方法通过以医院为基础的病例—对照研究方式,采用TaqMan-聚合酶链反应(TaqMan-PCR)技术分析1 499例HCC患者和2 045名对照者XRCC4第247密码子及XPC第939密码子的基因型,以二分类logistic回归和Cox比例风险模型分析XRCC4和XPC编码区突变与AFB1相关性HCC发病和预后的关系。结果①XRCC4和XPC编码区多态性增加HCC的发病风险(P<0.05),风险值分别为2.01和1.76;②XRCC4和XPC突变基因型与AFB1暴露在HCC发病中存在相乘交互作用;③XRCC4和XPC突变基因型调节HCC的预后。结论 XRCC4和XPC编码区突变增加AFB1相关性HCC的发病风险,并影响HCC的预后。

Objective To investigate the effects of mutations at coding regions of X-ray repair complementing group 4 （XRCC4） and xeroderma pigmentosum group C （XPC） on the development and prognosis of hepatocellular carcinoma （HCC） related to aflatoxin B1 （AFB1） exposure. Methods This study, including 1 499 HCC cases of HCC and 2 049 controls, was a hospital-based case-control study. TaqMan-PCR technique was employed to test genotypes of XRCC4 codon 247 and XPC codon 939, whereas logistic regression model and Cox＇s regression model were used to analyse the correlation of XRCC4 and XPC mutations with development and prognosis of AFB1-related HCC. Results The mutations at coding regions of XRCC4 and XPC gene increased the risk of development of HCC, with relative odd ratios of 2.01 and 1.76 for XRCC4 and XPC respectively （P 〈 0. 05）. The mutative genotypes of XRCC4 and XPC genes interacted with AFB1 exposure in development of HCC. Furthermore, the mutative genotypes of these two genes modified the prognosis of HCC. Conclusion The mutations at coding regions of XRCC4 and XPC may increase the risk of development of AFB1-related HCC and modulate the prognosis of HCC.