Association Between Autoimmune Diseases and Colorectal Cancer Risk: A Structured Narrative Review with Focused Meta-Analysis of Ulcerative Colitis and an Evidence-Gap Assessment of Psychological Stress and Anxiety

Abstract

Background: Autoimmune diseases may influence colorectal cancer (CRC) risk through chronic inflammation, treatment, surveillance, and disease-specific mechanisms. Psychological stress and anxiety may also affect cancer-related pathways through behavioral, neuroendocrine, immune, or health-care mechanisms.
Methods: A structured narrative-review framework, informed by PRISMA 2020 reporting conventions but based on backward and forward citation chasing rather than a complete multi-database export, assessed 31 source-linked records. Eight records were excluded (most often for an ineligible exposure, outcome, or study design), 23 reports underwent primary-evidence assessment, and 18 provided numeric data. Only exchangeable ulcerative colitis (UC) outcomes were pooled. Log standardized incidence ratios (SIRs) and incidence rates were analyzed using restricted maximum likelihood random-effects models with modified Hartung-Knapp confidence intervals. Heterogeneity, prediction intervals, and leave-one-out analyses were evaluated. Other autoimmune diseases and psychological evidence were synthesized narratively.
Results: Nine UC cohorts reported 1,848 CRC cases over 1,411,909.5 person-years; pooled incidence was 1.41 per 1,000 person-years (95% CI, 1.16-1.72; I² = 58.4%), the more stable and interpretable contemporary benchmark. Four UC cohorts contributed comparative SIRs. The pooled SIR was 2.86 (95% CI, 0.51–16.00; 95% prediction interval, 0.02–462.99; I² = 95.6%), an elevated point estimates whose prediction interval spans three orders of magnitude and therefore does not support a stable estimate of true effect in a new setting. Evidence for other autoimmune conditions varies by population, direction, and endpoint. Five psychological records were identified, but no eligible study jointly modeled autoimmune disease, psychological stress or anxiety, and incident CRC; mediation or effect modification could not be estimated.
Conclusions: Current evidence supports UC-focused meta-analysis and disease-specific interpretation of other autoimmune conditions. Psychological stress and anxiety cannot yet be established as mediators or modifiers of autoimmune-associated CRC risk, and their role remains unresolved rather than confirmed or excluded. Interpretation is limited by incomplete database searching, risk-of-bias assessment, and primary-source verification.