Impact of KRAS mutation on outcome of patients with metastatic colorectal cancer

Hepatogastroenterology. 2014 Oct;61(135):1946-53.

Abstract

Background/aims: KRAS mutation is present in 30%-50% of colorectal cancers and is associated with the inefficacy of anti-epidermal growth factor receptor therapy, while the impact of KRAS on survival is seldom discussed. The aim of this study was to elucidate the impact of KRAS status on the survival of patients with metastatic colorectal cancer.

Methodology: Two hundred and one patients with metastatic colorectal cancer were enrolled. Amplification and sequencing of the KRAS gene were performed, with the overall survival according to KRAS status analyzed.

Results: KRAS mutations were present in 72 (35.8%) of patients, including 55 (27.3%) codon 12 mutations and 17 (8.5%) codon 13 mutations. Lymphovascular invasion (hazard ratio 1.841, 95% confidence interval 1.043-3.247, p = 0.035) and KRAS mutation (hazard ratio 1.919, 95% confidence interval 1.104-3.333, p = 0.021) were independent prognostic factors for overall survival. The median overall survival for patients with KRAS mutation at codon 12 was 27.3 months, and was similar to those with KRAS mutation at codon 13 (20.4 months, p = 0.628).

Conclusions: KRAS mutation is a poor prognostic factor in patients with metastatic colorectal cancer. In KRAS mutation metastatic colorectal cancer, mutation at codon 12 or at codon 13 had no relationship with prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Codon
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / secondary*
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Risk Factors
  • ras Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Codon
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins