KRAS Mutation and Venous Thromboembolism Risk in Colorectal Cancer: A Danish Population-Based Cohort Study

Kirsten rat sarcoma viral proto-oncogene (KRAS) mutations may promote a prothrombotic state through tumor-related activation of coagulation pathways. However, evidence for an association with venous thromboembolism (VTE) in colorectal cancer (CRC) patients remains inconclusive. We examined the association between KRAS mutation status and VTE risk.

We conducted a population-based cohort study using Danish nationwide registries. We included patients diagnosed with stage I-IV CRC who underwent somatic KRAS mutation testing between 2015 and 2023. We computed 1-year risks of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) using the Aalen-Johansen method and calculated adjusted hazard ratios (HRs) using cause-specific Cox proportional hazards regression.

The study included 10,544 patients with CRC who underwent KRAS testing (4,602 [44%] with KRAS mutations; median age 71 years; 56% male). During one year of follow-up, 399 VTE events occurred. The 1-year risk of VTE was 4.6% (95% confidence interval [CI], 4.0-5.2) in the KRAS-mutated group and 3.1% (95% CI, 2.7-3.6) in the KRAS-wildtype group. The adjusted HR for VTE comparing KRAS mutations vs. wildtype was 1.37 (95% CI, 1.12-1.67), with estimates of 1.44 (95% CI, 1.13-1.84) for PE and 1.22 (95% CI, 0.85-1.75) for DVT. Substantial heterogeneity was observed across KRAS subtypes, with the highest hazards for unspecified codon 13 mutations (adjusted HR, 2.19; 95% CI, 1.38-3.46) compared with those with KRAS wildtype.

KRAS mutations were associated with an increased risk of VTE in patients with CRC who underwent KRAS testing.