Elevated relative risk of venous thrombosis in young adults with colorectal cancer: A global retrospective study

Abstract Colorectal cancer (CRC) is a major global health concern, with an annual incidence of 35.9 per 100,000 and a mortality rate of 13.1 per 100,000 between 2016-2020 in the United States. CRC incidence in younger adults (<55 years) has been steadily rising, increasing from 11% in 1995 to 20% in 2019, driven by a 1%-2% annual increase since the mid-1990s. Patients with CRC are known to have an increased risk of thrombosis but previous studies have reported a wide range in the relative risk of venous and arterial thrombotic events. A comprehensive, age-stratified analysis in a larger and diverse population is needed to better define thrombotic risk, particularly in the current era when CRC is increasingly diagnosed in younger individuals. Thus, we aimed to determine the global risk of venous and arterial thrombosis in patients with CRC, stratified by age, and tracked over a longitudinal follow-up period of up to five years. In this retrospective cohort study, we utilized the TriNetX de-identified electronic health record network that includes information on 150+ million patients from ∼106 participating health care centers across the world. Two cohorts were included: (1) adults diagnosed with CRC from July 2015 through July 2025, and (2) a control cohort that did not have a diagnosis of CRC or any neoplasm during the same time period. Cohorts were stratified according to age (young [18-50 yrs], middle-aged [51-64 yrs] and elderly [≥65 years]), and within each age-group propensity score matching was applied to control for age, common thrombotic confounders (overweight and obesity, diabetes, and hypertension), and use of antiplatelet/anticoagulant therapy. Our analysis assessed the risk of venous thromboembolism (deep vein thrombosis [DVT], and pulmonary embolism [PE]) and arterial thrombosis (acute myocardial infarction [MI]; and stroke) that occurred within 3 months, 6 months, 1 year, or 5 years post-diagnosis of CRC. The absolute risk and risk ratios (RR) with 95% confidence intervals (CI) were calculated for CRC versus control within each age-group. A total of 71,973 CRC patients aged 18–50, 158,663 aged 51–64, and 237,933 aged ≥65 were matched 1:1 to controls. The absolute risk of DVT and PE was significantly higher in CRC compared to control for all age-groups at each time-point. The RR for DVT and PE was increased in all age-groups at every-time point (2.32-6.38 and 2.84-10.32, respectively), with the highest relative risk observed in the youngest age group at 6-months for DVT (RR 6.38 with 95% CI 5.29, 7.71) and PE (RR 10.32 with 95% CI 8.31,12.81). In contrast to venous thrombosis, the relative risk for arterial thrombosis in CRC was lower; the RR for MI ranged from 0.962 to 1.345 and the RR for stroke was 0.649 to 0.940, suggesting a lower risk of MI and stroke in patients with CRC. We concluded that patients with CRC have a high risk of venous thromboembolism compared to matched controls, with the highest relative risk observed in young adults within 6 months of CRC diagnosis. The relative risk for arterial thrombosis was only modestly elevated for MI and no appreciable increase in risk for stroke was observed. These data suggest that young patients with CRC may need more careful monitoring and/or therapy for primary prevention of venous thrombosis.