细胞色素CYP2E1和GST M1与肺癌易感性的病例对照研究

目的探讨谷胱甘肽转硫酶(GST)和细胞色素CYP2E1多态性与肺癌易感性的关系.方法选取广州市广东籍新发肺癌病人91例及同期非肺部疾患及相同性别的病人91例作匹配,调查他们的吸烟、饮酒等因素的暴露情况.用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)技术检测CYP2E1和GST的基因多态性.结果CYP2E1 C1C1基因型与C1C2基因型比较,其OR为1.82(95%CI=0.95～3.40),GSTM1基因缺失型的OR值为1.26(0.69～2.30),而两者联合分析时,则可增加患肺癌的危险,其OR值为2.13(0.82～5.56),但无统计学意义(P＞0.05).吸烟与肺癌关系密切,其OR值为2.82(1.56～5.12),当吸烟与这两种基因型协同作用时,可明显提高患肺癌的危险性,携带CYP2E1 C1C1基因型的吸烟者的OR值为5.42(2.05～14.32),GSTM1基因缺失型的吸烟者的OR值为4.38(1.81～10.61).多因素logistic回归分析结果表明:文化程度(OR为0.63,0.45～0.86)、吸烟量(OR为1.56,1.14～2.14)、元抽油烟机(OR为3.77,1.48～9.56)、食用动物油(OR为1.67,1.25～2.24)、胡萝卜(OR为0.47,0.22～0.98)、饮酒(OR为6.58,1.53～28.3)、直系亲属肺癌史(OR为3.75,1.64～8.58)等因素与肺癌有关,而上述两种基因均未进入模型.结论CYP2E1和GSTM1在单因素分析中未显示出与肺癌风险的联系.这两种基因分别与吸烟协同作用时明显提高肺癌的危险性.然而在多因素分析中均未进入logistic模型,说明它们均不是肺癌个体易感性的主效基因,而是次效基因.

A case control study on the impact of CYP2E1 and GST-M1 polymorphisms on the risk of lung cancer

Objective To study the correlation of CYP2E1 polymorphism and GST-M1 polymorphism,independently and in combination,with the risk of lung cancer. Methods A case control study included 91 cases of lung cancer as the test group and 91 non-pulmonary disease cases as the control group. CYP2E1 Rsal and GST-M1 were analysed by PCR and RFLP. Results As CYP2E1 C1C1 genotype in compare with C1C2 genotype,the OR was 1.82(95% CI=0.95-3.40),the GST-M1 null(0/0) genotype gave an OR 1.26(0.69-2.30);if the two were analysed jointly,the lung cancer risk can be increased with an OR 2.13 (0.82 -5.56),but the difference had no statistical meaning ( P >0.05). Smoking was closely related to lung cancer,the OR was 2.82 (1.56-5.12). When smoking and the two above mentioned genotypes acted jointly,the lung cancer risk increased markedly;the CYP2E1 C1C1 genotype smokers had an OR 5.42(2.05-14.32),and the GST-M1 null (0/0) genotype smokers had an OR 4.38(1.81-10.61). The results of multivariate logistic regression analysis showed that seven factors were associated with lung cancer. They were higher education (OR 0.63,95% CI 0.45-0.86),amount of smoking (1.56,1.14-2.14),no kitchen smoke exhauster (3.77,1.48-9.56),consumption of animal oil (1.67,1.25-2.24),frequent consumption of carrot ( 0.47,0.22-0.98),alcohol drinking (6.58,1.53-28.3),and family lung cancer history (3.75,1.64-8.58). However,the two genotypes mentioned did not enter into this model. Conclusion In single factor analysis,CYP2E1 and GST-M1 did not associate with the risk of lung cancer. There was a synergic interaction by these two genotypes and the smoking in elevating the susceptibility to lung cancer. But since these two genotypes did not enter into the multivariate logistic regression model,it seems that they were not the major but a minor genetic susceptable factors for lung cancer.