MDR1 single nucleotide polymorphism G2677T/A and haplotype are correlated with response to docetaxel-cisplatin chemotherapy in patients with non-small-cell lung cancer

Respiration. 2009;78(1):49-55. doi: 10.1159/000158454. Epub 2008 Sep 24.

Abstract

Background: The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the expression and function of P-gp, thereby influencing the response to chemotherapy.

Objectives: To investigate whether the MDR1 2677 and 3435 genotypes are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to docetaxel.

Methods: In this study we investigated the potential association of MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were treated with docetaxel-cisplatin.

Results: The 2677 GG genotype was associated with a significantly better response to chemotherapy compared with the combined 2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated with a better response to chemotherapy compared with the combined 3435 CT and TT genotypes although the difference was not statistically significant (p = 0.123). Moreover, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015).

Conclusion: Our findings suggest that the MDR1 2677G>T/A polymorphism and the 2677G-3435C haplotype are predictors of treatment response to docetaxel-cisplatin chemotherapy in NSCLC patients.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Cisplatin / therapeutic use*
  • Docetaxel
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Taxoids / therapeutic use*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Cisplatin