Markedly Increased Risk of Colorectal Cancer and Decreased Risk of All Malignancies in Patients With Narcolepsy: A Nationwide Population-Based Cohort Study

Background and Objective In light of orexin-related gastrointestinal malignancy pathogenesis, we examined the risk of colorectal cancer in patients with type 1 narcolepsy (NT1).Methods Using the Korean National Health Insurance claims database (2010–2019), we enrolled all patients with NT1 (n=5,916) and, as controls, patients who underwent appendectomy without narcolepsy or idiopathic hypersomnia. The cohorts were matched 1:10 for sex, age, and comorbidities, and incidence rates and hazard ratios (HRs) for all malignancies and for colorectal malignancy were compared by multivariable analysis.Results The incidence of all malignancies was 664.1 (95% confidence interval, 660.6–667.6) in patients with NT1 versus 708.9 (692.4–725.7) in controls (p=0.0002), and the HR for any cancer was 0.65 (0.63–0.67) unadjusted and 0.67 (0.64–0.70) adjusted. The incidence of colorectal malignancy was 285.2 (283.3–288.1) versus 123.5 (112.4–125.9) (p<0.0001), the HR being 2.29 (2.14–2.44) unadjusted and 1.77 (1.48–2.11) adjusted.Conclusions Matched patients with NT1 showed an increased risk of colorectal malignancy but a lower risk of overall malignancy than appendectomy controls.