Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case–Control Study

SIMPLE SUMMARY: Early onset of colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. We investigated preexisting autoimmune and metabolic diagnoses of 2626 EOCRC patients in Sweden, diagnosed in 2007–2016, together with 15,756 controls matched for birth year, sex, and county. Comorbid diagnoses were collected from the National Patient Register. A history of metabolic disease nearly doubled the incidence of EOCRC, and presence of inflammatory bowel disease (IBD) was associated with a sixfold increased incidence of EOCRC. Patients with both IBD and metabolic disease had a lower incidence of EOCRC compared with IBD patients without metabolic condition. Non-IBD autoimmune disease was not associated with an increased incidence of EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines. ABSTRACT: Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case–control study, we included all EOCRC cases in Sweden diagnosed during 2007–2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66–1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78–7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57–5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.