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

Summary 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.