title: Tumor oncogene (KRAS) status and risk of venous thrombosis in patients with metastatic colorectal cancer.
abstract: 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.
  
  
  OBJECTIVE
  To determine if a tumor genetic characteristic, KRAS mutational status, is associated with an increased risk of VTE in patients with mCRC.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Vermont Cancer Center, University of Vermont, Burlington, VT, USA.
authors: S
authors: S
authors: Ades
authors: Department of Medicine, Vermont Cancer Center, University of Vermont, Burlington, VT, USA.
authors: S
authors: S
authors: Kumar
authors: The James, Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: M
authors: M
authors: Alam
authors: Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA.
authors: A
authors: A
authors: Goodwin
authors: New Hampshire Oncology-Hematology PA, Hookset, NH, USA.
authors: D
authors: D
authors: Weckstein
authors: New England Cancer Specialists, Scarborough, ME, USA.
authors: M
authors: M
authors: Dugan
authors: Department of Math and Statistics, University of Vermont, Burlington, VT, USA.
authors: T
authors: T
authors: Ashikaga
authors: The James, Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: M
authors: M
authors: Evans
authors: Department of Medicine, Vermont Cancer Center, University of Vermont, Burlington, VT, USA.
authors: C
authors: C
authors: Verschraegen
authors: Department of Medicine, Vermont Cancer Center, University of Vermont, Burlington, VT, USA.
authors: C E
authors: CE
authors: Holmes
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009511:New England / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000453:epidemiology*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000453:epidemiology*; D020246:Venous Thrombosis / Q000175:diagnosis / Q000453:epidemiology*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: cancer; colon cancer; pulmonary embolism; thromboembolism; venous thrombosis