Relationship Between Cytochrome P450 3A5 Gene Polymorphisms And Sensitivity To Cisplatin And Vinorelbine As First-line Chemotherapy In Advanced Non-Small Cell Lung Cancer

Objective: Cytochrome P450 is a heme-containing superfamily. It is a terminal oxidative enzyme of mixed-function oxidative enzyme system on endoplasmic reticulum (ER) and is widely distributed among human tissues and organs. It involves in biotransformation of internal materials, and activation and degradation of external materials. Research in pharmacological genetics shows that polymorphisms, which mean a minor difference in genome sequence, can lead to diverse capacities in drug metabolism and influence chemotherapeutic sensitivities. CYP3A5*3 is the most common polymorphism detected among Chinese .That may influence the efficacy of cisplatin and vinorelbine as first-line chemotherapy in advanced non-small cell lung cancer. We conducted a study to detected the genotype of these polymorphisms by PCR-RFLP in 96 patients with NSCLC and assessed their responses to cisplatin and Vinorelbine.Methods: In the study, we included 96 patients with advanced NSCLC who conformed by the Shandong Provincial Tumor Hospital pathlogy or cytology. Two milliliter of whole blood was collected from peripheral vein before chemotherapy, and DNA was extracted from these samples using the Puregene DNA Isolation kit.The DNA stored at -20℃until the analysis for this study. We conducted a study to detected the genotype of these polymorphisms by PCR-RFLP in 96 patients with NSCLC.All data were analyzed statistically using SPSS17.0 software. Count the statistical data usedχ2 test, P <0.05 was considered statistically significant.Results: 1. Genotype frequencies of polymorphisms of CYP3A5 Homozygous variant genotype (A/A) was present in 8(8.3%) of 96 patients, heterozygous variant genotype (A/G) was present in 43(44.8%), Wild type genotype (G/G) was present in 45(46.9%).2. The response rate to the chemotherapy in patients with wild type genotype(A/A)was 12.5%,but the response rate in patients with homozygous variant genotype (G/G) and heterozygous variant genotype (A/G) was 48.9%,there was a significant difference between them.(P=0.000,95%CI=0.000-0.031)3.The response rate to the chemotherapy in patients with homozygous variant genotype(G/G) were not significantly higher than that in patients with wild type genotype(A/A) and heterozygous variant genotype (A/G).(P=0.138, 95%CI=0.820 -4.189).Conclusions: The results suggest that patients with advanced NSCLC carrying CYP3A5 gene A/A,A/G and G/G genetypes have different efficence when they received vinorelbine and cisplatin chemotherapy. The response rate to the chemotherapy in patients with one *G allel at least were significantly higher than that in patients with wild-type homozygous(A/A).So CYP3A5 gene polymorphism has some significance in predicting the chemosensitivity about vinorelbine and cisplatin chemotherapy ,awhich is the first-line chemotherapy in advanced NSCLC.