Evaluating the risk of digestive system cancer in autoimmune disease patients: a systematic review and meta-analysis focusing on bias assessment.

Abstract

There is emerging evidence that certain autoimmune diseases can modulate the risk for digestive system cancer. However, limitations of non-experimental studies may lead to diverging results. Thus, the aim was to evaluate the available evidence and provide bias-minimized estimates for the associations between celiac disease (CD), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and type 1 diabetes (T1D) and different digestive system cancers. Systematic review (PROSPERO: CRD42024553216) was conducted according to PRISMA guidelines. Scientific publications were searched in PubMed, Web of Science, Embase, and Cochrane Library from inception up to May 2, 2025, with no restrictions on publication date. ROBINS-E tool was used for examining the study-specific risk of bias. Inverse-variance weighted random-effects models were performed as the primary meta-analytic approach. Heterogeneity was quantified and adjusted for in a comprehensive bias assessment including several analyses. This study included 237 estimates from 47 studies covering over 1.5 million cases of any ethnicity. CD, SLE, and T1D were positively associated with pancreatic, esophageal, colon, liver, and hepatobiliary cancers. Additionally, T1D was positively associated with stomach and colorectal cancers. The strongest bias-corrected association was found between CD and small intestine cancer (RR = 4.19; 95% CI: [2.71; 6.50]). MS was inversely associated with pancreatic, esophageal, rectal, and colorectal cancers. This study provides new insights into the evidence for digestive system cancer risk related to autoimmune diseases by adjusting for multiple sources of bias. As a next step, potential mechanisms responsible for the different associations should be investigated. The study received academic funding from the Faculty of Medicine, University of Augsburg, Germany.