谷胱甘肽硫转移酶M1和T1基因多态性与肺癌易感性关系的研究

目的和方法:采用病例-对照研究方法和多重PCR技术检测肺癌病例组161人和健康对照组165人的GSTM1(glutathioneS-transferaseM1)和GSTT1(glutathioneS-transferaseT1)基因缺陷型的频率,以多因素Logistic回归模型评价GSTM1和GSTT1基因型之间以及基因型与吸烟之间的交互作用。以探讨谷胱甘肽硫转移酶M1和T1的基因多态性与肺癌发病的关系。结果:GSTM1基因缺陷型和GSTT1基因缺陷型的频率在病例组和对照组之间均无显著的差异。在不吸烟(SI=0)的人群中,GSTM1基因缺陷型携带者患肺癌的危险性显著增加。此外,该基因型还可显著增加年龄≥60岁者患肺腺癌的危险性。多因素Logistic回归分析显示吸烟和GSTM1基因缺陷型是肺癌的危险因素,吸烟与GSTM1和GSTT1基因型不存在交互作用。分层分析表明GSTT1基因功能型与GSTM1基因缺陷型存在明显的交互作用,在年龄≥60岁的人群及不吸烟的人群中,GSTT1基因功能型可以使得GSTM1基因缺陷型携带者患肺腺癌的危险度分别降低48.5%和45.3%。结论:GSTM1基因缺陷型是非吸烟者和年龄≥60岁者患肺癌,尤其是患肺腺癌的危险因素,GSTT1基因功能型可以降低不吸烟或年龄≥60岁的GSTM1基因缺陷型携带者患肺腺癌的危险度。在肺癌的发生过程中GSTM1和GSTT1基因缺陷型与吸烟不存在交互作用。

Relationship between genetic polymorphisms of GSTM1 as well as GSTT1 and lung cancer

AIM and METHODS: To examine the relationship of glutathione S-transferase M1( GSTM 1) and T1( GSTT 1) with the occurrence of lung cancer, The case-control study was conducted among 161 lung cancer and 165 healthy controls. The genetic polymorphisms of GSTM1 and GSTT1 were detected with the method of multiplex polymerase chain reaction. Logistic regression analyses were used to assess the interaction of between different genotypes as well as between null genotypes and smoking. RESULTS: The frequences of GSTM 1 and GSTT 1 null genotypes had no obvious difference between lung cancer and healthy controls. In non-smoking subjects, the frequence of GSTM 1 null genotype was significantly different between lung cancer and healthy controls. Furthermore, GSTM 1 null genotype was significantly overrepresented in adenocarcinoma patients aged 60 or over, compared with controls.The results from interaction analyses showed although smoking and GSTM 1 deletion were associated with an increased risk of lung cancer, GSTM1 and GSTT 1 null genotypes combined with smoking did not have interaction effect on the risk of lung cancer. The risk for adnocarcinoma in the individuals at the age of 60 or over and in nonsmokers without GSTM1 gene but with GSTT1 functional genotype decreased by 48.5% and 45.3%, respectively. CONCLUSION: Our results suggest that GSTM1 deletion is an important host risk for lung cancer, and imply that GSTT1 functional genotype protects the old (aged 60 or over) and nonsmokers who are lack of GSTM1 gene from the risk of adenocarcinoma.