Tumor oncogene (KRAS) status and risk of venous thrombosis in patients with metastatic colorectal cancer

J Thromb Haemost. 2015 Jun;13(6):998-1003. doi: 10.1111/jth.12910. Epub 2015 Apr 23.


Background: Patients with metastatic colon cancer (mCRC) are at increased risk of venous thromboembolism (VTE). Limited preclinical data suggest that the oncogene (KRAS) mutational status of the tumor represents a plausible clinical link to systemic hypercoagulability in cancer patients.

Objectives: To determine if a tumor genetic characteristic, KRAS mutational status, is associated with an increased risk of VTE in patients with mCRC.

Patients/methods: A retrospective cohort study of patients with mCRC and KRAS test results was conducted at multiple practice sites across New England in the United States. The primary outcome was a VTE event, defined as deep venous thrombosis (DVT) and/or pulmonary embolism (PE), either 6 months before or at any time after the diagnosis of mCRC. KRAS status (mutated vs. wild type) and other relevant predictors of thrombosis were collected.

Results: Of 172 histologically confirmed patients with mCRC, 40 developed a VTE (23.3%). Sixty-five patients (37.8%) had a mutant KRAS status. The incidence of VTE and DVT among patients with mutated KRAS was 32.3 and 23.1%, respectively. The corresponding incidence among patients with wild-type KRAS was 17.8 and 9.4%. Odd ratios for the association were 2.21 (95% CI, 1.08-4.53) for VTE and 2.62 (95% CI, 1.12-6.12) for DVT, and remained significant despite adjustment for Khorana score and bevacizumab use.

Conclusion: Tumor mutant KRAS status is associated with an increased risk of VTE in patients with mCRC. The tumor genetic profile may represent a novel and important risk factor for thrombosis in patients with cancer.

Keywords: cancer; colon cancer; pulmonary embolism; thromboembolism; venous thrombosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • New England / epidemiology
  • Odds Ratio
  • Phenotype
  • Predictive Value of Tests
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Pulmonary Embolism / diagnosis
  • Pulmonary Embolism / epidemiology*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / epidemiology*
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / epidemiology*


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