G12V and G12C mutations in the gene KRAS are associated with a poorer prognosis in primary colorectal cancer

Int J Colorectal Dis. 2019 Aug;34(8):1491-1496. doi: 10.1007/s00384-019-03344-9. Epub 2019 Jul 15.

Abstract

Purpose: The increased incidence of colorectal cancer (CRC) has necessitated the development of novel prognostic and predictive factors from which new diagnostic tests could evolve. Evidence suggests the KRAS gene represents such a factor; its mutations are considered to be early indicators of CRC progression. This study assessed the prognostic impact of specific known KRAS codon 12/13 mutations on survival in patients with CRC.

Methods: Formalin-fixed paraffin-embedded tissue blocks or sections from primary were obtained from patients registered between 2014 and 2016 for genomic DNA extraction. KRAS gene was analyzed by direct sequencing or Luminex assay. The primary endpoint was the frequency of KRAS gene mutations and the secondary endpoints were differences in KRAS mutation rates by various stratification factors. Univariate and multivariate analyses were performed to investigate relationships between KRAS mutation rates and patient background factors.

Results: Sequencing of 200 CRC primary tumor samples demonstrated 74 (37.5%) with KRAS mutations in codons 12 (77%; 57/74) and 13 (23%; 17/74), all of which were TNM stages I-III. Tumors with KRAS mutations were more frequently located in the right side of the colon. Multivariate analysis indicated that G12V or G12C mutations were associated with poor prognosis [hazard ratio (HR) = 3.77, 95% confidence interval (CI), 1.54-8.39 and HR = 6.57; 95% CI, 1.90-17.7, respectively] in terms of recurrence-free survival.

Conclusion: KRAS codon 12G-to-V or G-to-C mutations are independent prognostic factors in patients with stage I-III CRC.

Keywords: Cancer; Colorectal; KRAS; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Codon / genetics
  • Colorectal Neoplasms / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Risk Factors

Substances

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