Association between polymorphisms of CYP3A5,MDR1,COX-2 and chemotherapy outcomes of advanced NSCLC / 国际肿瘤学杂志

ABSTRACT

Objective To investigate whether genotypes of CYP3A5,MDR1 and cyclooxygenase-2 are associated with the sensitivity of vinorelbine-platinum to NSCLC.Methods The genotypes of CYP3A5(*3),MDR1 (2677G>T at exon 21 and 3435C>T at exon 26 and their haplotypes),cyclooxygenase-2 (-1 195G>A) were determined by RFLP-PCR and chemotherapy responses were analyzed in 69 non-small-celllung cancer (NSCLC) Chinese Han patients.They received a combination chemotherapy of vinorelbine-cispla-tin.Chi-square test was used to investigate the potential association of genotype with chemotherapy response.OR and 95% C1 were calculated.Results The 3435 CC genotype was associated with a significantly betterchemotherapy response compared with the combined 3435 CT and 1Tr genotypes(P=0.033).The 2677 GG genotype was also associated with a significantly better chemotherapy response compared with the combined 2677 GT and IT genotype(P=0.012).Moreover.patients with the 2677 G-3435 C haplotype seemed to have a better response to chemotherapy compared with those with the other haplotypes(P=0.063).CYP3A5*3 was not likely to correlate with sensitivity of vinorelbine-platinum to NSCLC.Cyclooxygenase-2-1195G>A was likely to have better response to vinorelbine but not statistically significant(P=0.067).Conclusion Polymor-Dhisms of MDR1 3435 C>T and MDR1 2677 G>A/T can be used for predicting treatment response to vinorel-bine-cisplatin chemotherapy in NSCLC patients.