DNA修复基因XPD单核苷酸多态性和环境因素的交互作用与肝细胞癌的关联研究

目的 探讨XPD基因751、312位点单核苷酸多态性和环境因素的交互作用与肝细胞癌的关系.方法 采用以医院为基础的病例对照研究方法,运用TaqMan MGB荧光定昔实时PCR分析方法对病例组300例肝细胞癌患者和对照组312例非肿瘤患者进行XPD基因751和312位点的基因型分析.以非条件logistic回归模型分析比较各基因型在两组中分布频率的差异,以及基因多态性和环境因素的交互作用.结果 XPD基因751位点3种基因型AA、AC、CC在病例组和对照组中的分布差异无统计学意义(P>0.05),与携带XPD751野生纯合子AA基因型者比较,携带XPD751AC或CC基因型者患肝细胞癌风险无显著增加(P>0.05).XPD基因312位点3种基因型GG、GA、AA在病例组和对照组中的分布差异有统计学意义(P<0.01).与携带XPD312野生纯合子GG基因型者比较,携带XPD312 AA基因型个体罹患HCC的风险是携带XPD312 GG基因型的2.67倍(OR=2.67,95%CI:0.431～16.537),但差异无统计学意义;携带至少一个XPD312A等位基因的个体罹患肝细胞癌的风险是GG基因型的2.62倍(95%CI:1.626～4.222),且差异有统计学意义.交互作用分析结果表明XPD基因751位点多态性与吸烟、XPD基因312位点多态性与吸烟、XPD基因312位点多态性与HBsAg阳性之间在肝细胞癌发生中存在交瓦作用,交互作用的OR值分别为4.291、5.341、7.348.结论 DNA修复基因XPD312A等位基因可能是广西南部地区人群肝细胞癌的危险等位基因,XPD基因多态性与吸烟、HBsAg阳性之间在肝细胞癌发生中存在交互作用,能增加罹患肝细胞癌的风险.

Study on the relationship between hepatocellular carcinoma and the interaction between polymorphisms in DNA repair gene XPD and environmental factors

Objective To study the relationship between hepatocellular carcinoma and the interaction of polymorphisms in DNA repair gene XPD with environmental factors. Methods A hospital-based ease-control study on hepatoeellular carcinoma was conducted. All the hepatocellular carcinoma eases (n=300) were newly diagnosed and controls (n=312) were diagnosed with non-tumor cases. XPD genotype (Lys751 Gin and Asp312 Ash) from blood derived DNA was determined using TaqMan MGB Real-time PCR. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results For XPD condon 751 genotypes, there was no significant difference between frequencies of the AC or CC among patients and controls (P>0.05) (referent AA). The frequency of XPD312A allelic gene was higher in eases than that in controls and was associated with an increased risk (adjusted OR = 2.62,95% CI: 1.626-4.222) for hepatocellular carcinoma when compared with GG genotype. Interactions were found between infection of HBsAg and XPD312 (OR=7.348), as well as between smoking and non-wild type gene of XPD751 (0R=4.291) and XPD312 (OR=5.341). Conclusion DNA repair XPD312A allelic gene might increase the risk of Hepatocellular carcinoma. Interactions between HBsAg infection, smoking and XPD were observed in Hepatocellular carcinoma.