Incidence and relative risk of colorectal cancer in autoimmune diseases: a global pooled-analysis with more than 91 million participants.

[BACKGROUND] Dysregulation of immune system could be a vital stimulant of colorectal cancer development. We aimed to provide the most comprehensive meta-analysis on this topic.

[METHODS] Observational cohort studies reporting incidence or risk ratio of colorectal cancer among patients with autoimmune disorders as exposures were eligible. Relative risk was the primary endpoint and adjusted risk ratio were effect sizes. Incident cases per 100 000 person-years at risk were used for incidence analysis as secondary endpoint.

[RESULTS] 523 studies were included, containing 91 265 886 participants. Overall pooled risk ratio was 1.244 ( p < 0.001). The results were consistent irrespective of sub-localization (colon: 1.308, p < 0.001; rectum: 1.173, p < 0.001), sex (male: 1.229, p < 0.001; female: 1.209, p < 0.001) and country (Nordic: 1.301, p < 0.001; Western: 1.213, p < 0.001; East Asian: 1.213, p < 0.001). Specifically, primary sclerosing cholangitis, idiopathic inflammatory myopathies, inflammatory bowel disease, autoimmune hepatitis, ANCA-associated vasculitis, sarcoidosis, scleroderma, type 1 diabetes, psoriasis, membranous nephropathy, hidradenitis suppurativa and idiopathic thrombocytopenic purpura were associated with higherrisk of colorectal cancer. Interestingly, several autoimmune diseases might help to lower colorectal cancer risk, especially rheumatoidarthritis.

[CONCLUSIONS] Patients with autoimmune diseases were associated with higher risk of colorectal cancer under generally or specific settings. Unlike ourgastric and small bowel cancer pooled results, this risk-increasing impact on colorectal cancer was consistent across Nordic, Western and East Asian countries. Both digestive organ-specific or systemic autoimmune diseases could significantly increase risk of colorectal cancer. However, several autoimmune diseases might act as protective factors against colorectal cancer, especially rheumatoid arthritis, while not on gastric or small bowel carcinogenesis.