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NQO1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

Relationship between hepatocellular carcinoma and the interaction between NQO1 polymorphisms and environmental factors

摘要:

目的 研究NQO1基因多态性和环境因素的交互作用与肝细胞癌易感性的关系. 方法 采用以manbet官网登录 为基础的病例对照研究方法,运用TaqMan MGB荧光定量实时PCR分析方法对病例组400例肝细胞癌患者和对照组400例非肿瘤患者进行NQO1基因C609T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 NQO1基因C609T位点CC、CT和TT各基因型频率分别为23.75%、50.25%和28.00%,对照组中3种基因型频率分别为37.55%、43.75%和18.25%,差异有统计学意义(P<0.05).与CC基因型相比,CT或者TT基因型的个体罹患HCC的风险OR分别为2.106(95%CI:1.137~3.110)和2.564(95%CI:1.357~4.744).T等位基因携带者患肝细胞癌的危险性是C等位基因携带者的1.86倍(OR=1.86,95% CI:1.235 ~ 2.980).交互作用分析结果表明NQO1基因多态性与肿瘤家族史、HBsAg阳性之间在肝细胞癌发生中存在交互作用,交互作用的OR值分别为2.431、8.359. 结论 NQO1C609T基因型可能是广西南部地区人群患肝细胞癌的危险因素之一,NQO1基因多态性与肿瘤家族史、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.

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Objective To study the relationship between hepatocellular carcinoma (HCC) and the interaction of polymorphisms in the NAD(P)H:quinone oxidoreductase (NQO1) gene with environmental factors using a hospital-based case-control study.Methods Four-hundred newly diagnosed HCC cases and 400 healthy individuals (non-tumor controls) were enrolled in the study.Demographic information and medical history was obtained by questionnaire.TaqMan minor groove binder real-time PCR was carried out to detect the NQO1 C609T genotype using blood-derived DNA from all study participants.Unconditional logistic regression analysis was carried out to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).Results The frequencies of NQO1 609 CC,CT and TT genotypes were 23.75%,50.25% and 28.00% in the HCC group,and 37.55%,43.75% and 18.25% in the control group.The differences between the HCC and control group reached statistical significance (all P < 0.05).The ORs of NQO1 609 CT and TT genotypes were significantly higher compared to the CC genotype; the adjusted OR(95% CI) of CT was 2.106(1.137-3.110) and of TT was 2.564(1.357-4.744).Individuals carrying the NQO1 609 T allelic gene had a significantly higher risk of HCC than those carrying the C allelic gene; the adjusted OR(95% CI) was 1.86(1.235-2.980).Interactions were found between hepatitis B virus infection with hepatitis B surface antigen (HBsAg)-positivity and NQO 1 gene polymorphisms (adjusted OR:2.431) and history of cancer (adjusted OR:8.3592).Conclusion The NQO1 C609T genotype is associated with increased risk of HCC.Interactions between HBsAg-positive infection,history of cancer,and NQO1 gene polymorphisms may contribute to HCC.

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