MDR1 single nucleotide polymorphisms predict response to vinorelbine-based chemotherapy in patients with non-small cell lung cancer

Respiration. 2008;75(4):380-5. doi: 10.1159/000108407. Epub 2007 Sep 12.


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 chi(2) 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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Cyclooxygenase 2 / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use
  • Vinorelbine


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Vinblastine
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Cisplatin
  • Vinorelbine