Venous thromboembolism and 20-year cancer risk: a Danish population-based cohort study.

Background: Venous thromboembolism (VTE) is associated with an elevated short-term cancer risk, but data on the long-term risk are conflicting. The mechanisms linking patients with VTE to elevated long-term cancer risk remain largely unknown. Objectives: To investigate long-term cancer risk after VTE and whether this risk pertained predominantly to cancers sharing risk factors with VTE. Methods: Using nationwide Danish registries, we followed patients with first-time VTE (1996-2022) until cancer diagnosis, death, emigration, or December 31, 2022, whichever occurred first. We used the Aalen-Johansen estimator to compute cumulative cancer incidence, treating death as a competing event. Standardized incidence ratios (SIRs) compared observed events with expected events based on general population rates. We analyzed cancer incidence overall and by site-specific and etiology groups for smoking-, obesity-, alcohol-, hormone-, and infection-related cancers, and "all other" cancers. Results: We followed 138,049 patients for a median of 5.5 years. The 1-year cancer risk was 4.0%. The 1-year SIR was 3.45 (95% CI, 3.36-3.55), then ranged from 1.09 to 1.16 over 20 years of follow-up, reaching 1.00 (95% CI, 0.90-1.11) thereafter. SIR was elevated in all cancer groups within 1 year and afterward, but was driven by site-specific cancers often related to smoking, obesity, and alcohol (lung, pharynx, larynx, esophagus, stomach, liver, pancreas, and colon), as well as hematological cancers. Conclusion: Compared with the general population, patients with VTE had an increased cancer risk for up to 20 years. Shared risk factors, such as lifestyle-related factors and genetic predisposition, may contribute to this increased risk.