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

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 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 better than on those carrying other types (P<0.001). 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 null-type 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 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