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

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International Journal of Colorectal Disease Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 183-8605, Japan

    Tamuro Hayama, Yojiro Hashiguchi, Yuka Okada, Kohei Ono, Ryu Shimada, Tsuyoshi Ozawa, Takeshi Tsuchiya, Hisae Iinuma, Keijiro Nozawa & Keiji Matsuda

  2. Department of Surgery, National Defense Medical College, Saitama, Japan

    Koichi Okamoto

  3. Department of Surgery, Nippon Medical School, Tokyo, Japan

    Tetsutaka Toyoda

Authors
  1. Tamuro Hayama
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  2. Yojiro Hashiguchi
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  3. Koichi Okamoto
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  4. Yuka Okada
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  5. Kohei Ono
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  6. Ryu Shimada
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  7. Tsuyoshi Ozawa
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  8. Tetsutaka Toyoda
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  9. Takeshi Tsuchiya
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  10. Hisae Iinuma
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  11. Keijiro Nozawa
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  12. Keiji Matsuda
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Corresponding author

Correspondence to Tamuro Hayama.

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The present study was conducted in accord with the Declarations of Helsinki and was approved by the Ethics Committee of the Teikyo University.

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Hayama, T., Hashiguchi, Y., Okamoto, K. et al. G12V and G12C mutations in the gene KRAS are associated with a poorer prognosis in primary colorectal cancer. Int J Colorectal Dis 34, 1491–1496 (2019). https://doi.org/10.1007/s00384-019-03344-9

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  • DOI: https://doi.org/10.1007/s00384-019-03344-9

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