The Role of KRAS Mutation in Colorectal Cancer-Associated Thrombosis

Int J Mol Sci. 2023 Nov 29;24(23):16930. doi: 10.3390/ijms242316930.

Abstract

Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE.

Keywords: KRAS; arterial and venous thrombosis; colorectal cancer; molecular subtypes.

MeSH terms

  • Anticoagulants / therapeutic use
  • Colorectal Neoplasms* / complications
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Humans
  • Mutation
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Retrospective Studies
  • Thrombosis* / genetics
  • Venous Thromboembolism* / genetics

Substances

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

Grants and funding

This work was partially supported by the “Carol Davila” University of Medicine and Pharmacy Bucharest, Romania through contract no. 33PFE/30.12.2021.