细胞色素P450基因多态性与肺癌易感性的相关性分析  

Combined Effects of Genetic Polymorphisms in Cytochrome P450s and GSTM1 on Lung Cancer Susceptibility

作　　者：顾艳斐[1] 张宗德[2] 张树才[1] 郑素华[3] 贾红彦[2] 古淑香[2] 

机构地区：[1]北京胸科医院肿瘤内科,北京101149 [2]北京胸科医院内科实验室,北京101149 [3]北京胸科医院流行病学研究室,北京101149

出　　处：《结核病与胸部肿瘤》2008年第1期16-21,共6页Tuberculosis and Thoracic Tumor

基　　金：首都医学发展科研基金资助项目（2002-3069）

摘　　要：目的 探讨代谢活化酶细胞色素P4501A1（CYP1A1）、2D6（CYP2D6）、2E1（CYP2E1）和代谢解毒酶谷胱甘肽硫转移酶（GSTM1）与肺癌易感性的关系。方法采用PCR、PCR—RFLP技术检测原发性肺癌组（279例）及对照组（684例）的CYPlAI、CYP2D6、CYP2E1、GSTM1代谢酶基因型，对不同基因型在两组分布频率的差异进行OR值的统计分析。结果CYPlAl突变等位基因（m）、GSTMl功能缺失型（-）分别可使患肺癌的危险性增加1．64（OR=1．64，95％CI为1．21—2．22，P=0．001）和1．58倍（oR=1．58，95％CI为1，19—2．11，P=0．002）。其中CYPlAl与肺鳞癌、小细胞癌，GSTMl与肺鳞癌及肺腺癌明显相关（均P〈0．05）。同时携带GSTMI（-）和CYPlAl（m）可使患肺癌的危险性明显增加（OR=2．75，95％CI为1．73～4．39，P=O．OOO）。在重度吸烟人群携带GSTMl（-）、CYPlAl（m）、CYP2D6（W）或CYP2ElA基因型均可使患肺癌的危险性显著增加5．71—11．67倍（辟O．000）。结论携带GSTMI（-）及CYPlAl（m）等位基因型者患肺癌的危险性上升，二者有协同作用。在重度吸烟人群，CYP及GSTMl的检测有利于发现肺癌的高危人群。Objective To investigate the relationship between the gene polymorphism of metabolizing enzymes and the genetic sus- ceptibility to lung cancer as well as to study the synergistic effects between smoking and the genes. Methods Peripheral blood samples were collected from 279 patients with primary lung cancer and 684 age-, nationality-, and native place-matched controls, including patients with benign diseases and healthy volunteers. PCR-RELP was used to detect the distribution of CYP1A1, 2D6,2El, and GSTMl genotypes. The correlation of these genes with the sensibility to lung cancer was analyzed. Results The CYP1A1 variant allele frequency of the lung cancer group was 67.4%,significantly higher than that of the control group （ 55.7%, P = O. 001 ） .GSTMI-nu11 genotype was found to be associated with lung cancer （OR=l.55,P=0.002）. The risk of lung cancer in the individuals carrying GSTMI-null genotype and CYP1A1 （w/m, m/m） genotype was 2. 75 times that of the individuals not carrying these genotypes （P〈0.01）. There were no significant differences in the frequencies of CYP2D6 and CYP2E1 genotypes between these two groups. In the heavy smokers GSTMI-null, CYP1A1, CYP2D6, and CYP2E1 genotypes increased the risk of lung cancer by 5.71-11.67 times （P=0.000）. Conclusion The individuals who carry GSTMI-null genotype and CYP1A11 （m） genotype have an increase risk of lung cancer. The combined effect of I phase metabolizing enzymes and Ⅱ phase metabolizing enzymes is observed.In heavy smokers the polymorphism of GSTM1 and CYPs affects the susceptibility to lung cancer.

关 键 词：肺肿瘤 细胞色素P-450 多态性 限制性片段长度 

分 类 号：R384.1[医药卫生—医学寄生虫学] R734.2[医药卫生—基础医学]