ERCC1 codon 118 C→T polymorphism associated with ERCC1 expression and outcome of FOLFOX-4 treatment in Asian patients with metastatic colorectal carcinoma

Cancer Sci. 2009 Feb;100(2):278-83. doi: 10.1111/j.1349-7006.2008.01031.x.

Abstract

We analyzed the influence of codon 118 C→T polymorphism of ERCC1 on its protein expression levels, clinicopathological features, and outcome of 168 Chinese patients with metastatic colorectal carcinoma that had been treated with first-line FOLFOX-4 chemotherapy. A high prevalence of C/C genotype was noted (47.6%, n = 80; 168 patients in total). A marked increase of ERCC1 protein expression levels was also noted in patients with C/T or T/T genotypes (70%vs 20%; P < 0.01), which was associated with significantly lower response to FOLFOX-4 (36.4%vs 57.5%; p = 0.01), and shorter progression-free (7 months vs 13 months; P < 0.01) and overall (16 months vs 25 months; P < 0.01) survival times. By multivariate analysis, this polymorphism was also identified as an independent prognostic factor (P = 0.02). These data suggest that Asian populations have a significantly higher prevalence of the C/C genotype in ERCC1 codon 118, which could be a key determinant for good responses to oxaliplatin-based treatment and favorable outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian Continental Ancestry Group / genetics*
  • Codon / genetics*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / secondary
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Endonucleases / genetics*
  • Endonucleases / metabolism
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Immunoenzyme Techniques
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / therapeutic use
  • Polymorphism, Genetic / genetics*
  • Survival Rate
  • Treatment Outcome

Substances

  • Codon
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • ERCC1 protein, human
  • Endonucleases
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol