CYP450 polymorphisms predict clinic outcomes to vinorelbine-based chemotherapy in patients with non-small-cell lung cancer

Acta Oncol. 2007;46(3):361-6. doi: 10.1080/02841860600902197.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • China / epidemiology
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • Gene Frequency / drug effects
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / drug effects*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / drug effects
  • Predictive Value of Tests
  • Survival Analysis
  • Treatment Outcome
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use
  • Vinorelbine

Substances

  • Antineoplastic Agents, Phytogenic
  • Vinblastine
  • Cytochrome P-450 Enzyme System
  • Vinorelbine