Associations of autoimmune diseases with appendiceal cancer in a population-based study.

Abstract

e16495 Background: Appendiceal cancer has a fast rising incidence, especially in younger adults. Causal factors of appendiceal cancers are unknown. There is immune dysregulation in appendiceal cancers, which is relevant given the significance of the appendix in mucosal immune regulation. We hypothesized that autoimmune and benign thyroid conditions, potentially including under-recognized autoimmune thyroiditis, are associated with appendiceal cancer. Methods: Using the All of Us Research Program (v8), a large, diverse U.S. cohort integrating electronic health record and survey data, we conducted a population-based study comparing adults with appendiceal adenocarcinoma to cancer-free controls. Autoimmune diseases were identified using ICD codes, and thyroid disorders were classified as autoimmune (Graves’ disease, Hashimoto’s thyroiditis) or benign (all other non-autoimmune thyroid disorders). Controls were adult participants with electronic health record and demographic data and no history of primary malignancy. Age- and sex-adjusted logistic regression estimated odds ratios (ORs). Results: Among 203 appendiceal cancer cases and 327,591 cancer-free controls, cases had a higher prevalence of any autoimmune disease (18.7% vs 10.2%, p<0.001), inflammatory bowel disease (IBD), autoimmune thyroid disease, rheumatoid arthritis (RA), and benign thyroid disorders (32.5% vs 11.2%) (all p<0.01). In age- and sex-adjusted analyses (Table), appendiceal cancer was associated with multiple immune-mediated conditions, most strongly IBD, as well as with non-autoimmune thyroid disorders. Additional associations were observed for RA, autoimmune thyroid disease, type 1 diabetes, and any autoimmune disease. Conclusions: Autoimmune diseases and non-autoimmune thyroid diseases are associated with appendiceal cancer in age- and sex-adjusted models in this cohort. Further investigation into immune-mediated and thyroid-related pathways contributing to the causal pathway of appendiceal cancer is essential, especially given other published data suggesting a parallel rapidly increasing incidence of these diseases. Prevalence and adjusted associations with appendiceal cancer. Condition Cases (%) Controls (%) Adjusted OR (95% CI) p-value Any autoimmune disease 38 (18.7%) 33,372 (10.2%) 1.92 (1.33-2.71) <0.001 IBD ≤20 4,852 (1.5%) 3.82 (1.95-6.67) <0.001 RA ≤20 8,030 (2.5%) 2.40 (1.29-4.07) 0.003 Type 1 diabetes ≤20 5,844 (1.8%) 2.24 (1.01-4.25) 0.026 Autoimmune thyroid disease ≤20 6,558 (2.0%) 2.37 (1.17-4.27) 0.008 Benign thyroid disorders 66 (32.5%) 36,814 (11.2%) 3.47 (2.54-4.72) <0.001