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CYP2C19*2(G681A), CYP2C19*3(G636A), CYP2D6*4(C188T), CYP2D6*2(C2938T, G4268C), CYP3AP1*3- G44A and CYP3A5*3(A22893G) are the most common polymorphisms detected among Chinese that may influence the efficacy of vinorelbine-based therapies to treat non-small-cell lung cancer (NSCLC). We detected the genotypes of these polymorphisms by PCR-RFLP in 59 patients with NSCLC and assessed their responses to vinorelbine. CYP2D6*4(C188T), CYP3AP1*3 (G -44 A) and CYP3A5*3 were found to be associated with response to vinorelbine. For the 2D6*4 polymorphism, the 18 of 32 (56.25%) patients with homozygous (C/C) responded to this therapy, while 6 of 27 (22.22%) of those heterozygous (C/T) at this site responded. (chi2=5.68, p < 0.05) For the 3AP1*1/*3 polymorphism, 12 of 42 (28.57%) patients with homozygous (A/A) responded, while 12 of 17 (70.59%) with heterozygous (A/G) and homozygous (G/G) responded (chi2=7.19, p < 0.01). CYP3A5*3 polymorphism has a result corresponding to 3AP1*3 polymorphism. Other polymorphisms were not associated with response to vinorelbine. No significant difference in toxicity and survival was observed according to SNP genotype.

Background: The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine. Objectives: To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC). Methods: We determined the genotypes of CYP3A5(*3), MDR1 (2677G→T at exon 21 and 3435C→T at exon 26 and their haplotypes) and COX-2 (–1195G→A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The χ2 test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated. Results: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435-2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (–1195G) is likely to result in a better response to vinorelbine (nonsignificant). Conclusions: Our findings suggest that MDR1 2677G→T/A and 3435C→T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients.