Ⅰ、Ⅱ相药物代谢酶遗传多态性与晚期非小细胞肺癌化疗疗效的关系  

Relationship between the Genetic Polymorphisms of Phase Ⅰ and Ⅱ Drug-metabolizing Enzymes,as well as the Outcome of Chemotherapy in Advanced Non-small Cell Lung Cancer

作　　者：李伟英[1] 岳文涛[1] 杨学惠[1] 张春彦[1] 王玥[1] 

机构地区：[1]北京市结核病胸部肿瘤研究所细胞生物学研究室,北京101149

出　　处：《中国肺癌杂志》2011年第11期858-864,共7页Chinese Journal of Lung Cancer

摘　　要：背景与目的目前药物代谢酶遗传多态性与化疗疗效关系的研究结果多不一致,本研究旨在探讨细胞色素P4501A1(cytochrome P450 1A1,CYP1A1)、2E1(cytochrome P450 2E1,CYP2E1)、2D6(cytochrome P450 2D6,CYP2D6)和谷胱甘肽硫转移酶M1(glutathione S-transferase M1,GSTM1)基因多态性与晚期非小细胞肺癌化疗疗效以及与肺癌患者预后的关系。方法采用PCR和PCR-RFLP技术对肺癌患者4种药物代谢酶基因分型,并对他们进行5年跟踪随访。结果携带B型CYP1A1和缺陷性GSTM1肺癌患者比其它基因型患者化疗疗效好(P<0.001)。携带A型CYP1A1肺癌患者接受非铂类化疗药物治疗比B型和C型患者疗效好(P=0.041);携带缺陷性GSTM1肺癌患者接受铂类化疗药物治疗疗效比功能型患者疗效好(P=0.011)。4种酶对晚期非小细胞肺癌患者总生存期(overall survival,OS)没有明显影响(P>0.05)。结论 A型CYP1A1肺癌患者接受非铂类化疗药物治疗比B型和C型患者疗效好;缺陷性GSTM1肺癌患者接受铂类化疗药物治疗比功能型患者疗效好。4种酶基因多态对晚期非小细胞肺癌患者OS影响没有明显统计学差异。Background and objective Currently available studies on the polymorphisms of drug-metabolizing enzymes and their chemotherapeutic effects in non-small cell lung cancer are not consistent.In the present study,the rela-tionship of the gene polymorphisms of cytochrome P450 1A1 （CYP1A1）,cytochrome P450 2E1 （CYP2E1）,cytochrome P450 2D6 （CYP2D6）,and glutathione S-transferase M1 （GSTM1） enzymes with chemotherapeutic effects were investigated.the effects of these relationships on the survival of advanced non-small cell lung cancer patients were also examined.Methods Four drug metabolism enzymes were genotyped in lung cancer patients by polymerase chain reaction （PCR） and PCR-restriction fragment length polymorphism.These patients were followed for five years.Results The chemotherapeutic effect on patients carrying B-type CYP1A1 and null-type GSTM1 was be er than on those carrying other types （P0.001）.the chemotherapeutic effect on patients carrying A-type CYP1A1 was better than on those carrying the B and C types when non-platinum drugs were administered （P=0.041）.the chemotherapeutic effect on patients carrying nulltype GSTM1 was be er than on those carrying the functional type when platinum drugs were administered （P=0.011）.e four enzymes did not a ect the overall survival （OS） of advanced non-small cell lung cancer patients （P0.05）.Conclusion The chemotherapeutic effect on patients carrying A-type CYP1A1 was better than on those carrying the B and C types when non-platinum drugs were administered.the chemotherapeutic effect on patients carrying null-type GSTM1 was better than on those carrying the functional type when platinum drugs were administered.the four enzymes did not affect the OS of advanced non-small cell lung cancer patients.

关 键 词：肺肿瘤 药物代谢酶 化疗效果 预后 

分 类 号：R734.2[医药卫生—肿瘤]