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

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（cytochromeP4501A1，CYPlAl）、2El（cytochromeP4502El，CYP2E1）、2D6（cytochromeP4502D6，CYP2D6）和谷胱甘肽硫转移酶M1（glutathioneS-transferaseM1，GSTMI）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CYPlAl和缺陷性GSTMl肺癌患者比其它基因型患者化疗疗效好（P＜0．001）。携带A型CYPlAl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GSTMl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=O．011）。4种酶对晚期非小细胞肺癌患者总生存期（overallsurvival，OS）没有明显影响（R，O．05）。结论A型CYPIAI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GSTMl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 relationship of the gene polymorphisms of cytochrome P450 1AI（CYPIA1）, cytochrome P450 2EI（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 CYPIA1 and null-type GSTM1 was better than on those carrying other types （P〈0.001）. The chemotherapeutic effect on patients carrying A-type CYPIA1 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 better than on those carrying the functional type when platinum drugs were administered （P=-0.011）. The four enzymes did not affect the overall survival （OS） of advanced non-small cell lung cancer patients （P〉0.05）. Conclusion The chemotherapeutic effect on patients carrying A-type CYPIA1 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.