Colorectal cancer, comorbidity, and risk of venous thromboembolism: assessment of biological interactions in a Danish nationwide cohort

Background: Venous thromboembolism (VTE) is a major source of morbidity and mortality in cancer patients. Incident colorectal cancer (CRC) and comorbidity both predict VTE, but potential synergy between these factors has not been explored. Methods: Danish nationwide cohort study of CRC cases diagnosed in 1995-2010 and a matched general population reference cohort of subjects without CRC who matched cases on age, sex, and comorbidities. We calculated the Charlson Comorbidity Index using diagnoses recorded in the Danish National Patient Registry. We calculated standardised incidence rates (SIRs) and interaction contrasts (IC) to measure additive interaction between comorbidity and CRC status with respect to 5-year VTE incidence. Results: Among 56 189 CRC patients, 1372 VTE cases were diagnosed over 145 211 person-years (SIR = 9.5 cases per 1000 personyears). Among 271 670 reference subjects, 2867 VTE cases were diagnosed over 1 068 860 person-years (SIR = 2.8 cases per 1000 person-years). CRC and comorbidity were positively and independently associated with VTE, but there was no evidence for biological interaction between these factors (e.g., comparing the 'severe comorbidity' stratum with the 'no comorbidity' stratum, IC = 0.8, 95% CI: - 3.3, 4.8). Conclusions: There is neither a deficit nor a surplus of VTE cases among patients with both comorbidity and CRC, compared with rates expected from these risk factors in isolation.