吸烟和CYP1A1、GSTM1基因多态对肺癌易感性影响

Influence of smoking and the polymorphisms of CYP1A1 and GSTM1 on the susceptibility of lung cancer

目的:探讨细胞色素P4501A1(cytochrome P-4501 A1,CYP1A1)与谷胱甘肽硫转移酶M1(glutathione Stransferase M1,GSTM1)基因多态与支气管肺癌的关系。方法:采用PCR限制性片段多态检测法,检测肺癌组103例和正常对照组138例患者的CYP1A1与GSTM1基因多态,以非条件性Logistic回归模型分别对年龄、性别进行校正后计算优势比及95%CI。结果:CYP1A1m1突变型等位基因频率在对照组和肺癌组分别为27.6%和42.7%;GSTM1的缺陷型基因(D)频率在对照组、肺癌组分别为44.2%和61.2%。Logistic回归分析表明,CYP1A1(w1/m1)杂合型(B型)患肺癌的升高3.19倍,纯合突变型(C型)基因患肺癌的升高2.61倍,GSTM1缺陷型(D)患肺癌危险度升高2.09倍,差异均有统计学意义(P<0.05)。GSTM1(D)/CYP1A1(B或C)基因型的个体患肺癌危险度为5.72倍。GSTM1(D)和CYP1A1 m1突变型等位基因均可明显增加鳞癌和小细胞癌的患病危险度。结论:CYP1A m1突变型等位基因和GSTM1(D)均是患肺癌的危险因素。CYP1A m1突变型等位基因和GSTM1(D)存在明显的交互作用,二者与吸烟有协同作用。

Objective To study the relationship of cytochrome P-450 1A1（CYP1A1） and glutathione S-transferase M1 （GSTM1） polymorphisms with occurrence of lung cancer.Methods PCR-RFLP was used to determine genetic polymorphisms of CYP1A1 and GSTM1 in 103 patients with lung cancer and 138 healthy controls.Logistic regression analysis was used to assess the value of odds ratio （OR） and confidential intervals （CI） between different genotypes and smoking after adjusted by ages and gender.Results The allele frequencies of CYP1A1 M1 were 27.6% and 42.7% in control and lung cancer groups,respectively.The allele frequencies of GSTM1 deletion were 44.2% and 61.2% in control and lung cancer groups,respectively.OR for the CYP1A1 （B） or （C） genotype indicated 3.19 and 2.61-fold increased risk for developing lung cancer.The adjusted OR of the GSTM1 deletion genotype showed a 2.09-fold increased risk for lung cancer.Both associations were statistically significant.The increased risk for developing lung cancer was 5.72 folds for the individuals with combination of the CYP1A1（B or C） and GSTM1 deletion genotypes.CYP1A1 M1 and the GSTM1 deletion genotypes increased risk for developing small cell carcinoma and squamous carcinoma,significantly.Conclusion The mutant genotypes of the CYP1A1 M1 and GSTM1 deletion polymorphisms are the risk for lung cancer.CYP1A1 M1 and GSTM1 interact obviously,both of which have the joint effect with smoking.