In a systematic review and meta-analysis published in the journal eClinicalMedicine, Reizner et al highlighted bias-minimized insights into the associations between autoimmune diseases, such as celiac disease, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes, and the risk of various types of digestive system cancers.
“Our findings support the hypothesis of chronic inflammation (from autoimmunity) driving malignancy in specific organs, consistent with the literature on chronic inflammation and cancer,” the investigators commented. “The results of the present study are valuable for health-care professionals, as they highlight the importance of regularly monitoring patients with [the abovementioned autoimmune diseases] and conducting individualized cancer screening.”
Study Details
The investigators conducted a literature search in the PubMed, Embase, Cochrane Library, and Web of Science databases to identify English or German language–written peer-reviewed publications of observational studies (without cross-sectional studies) that presented risk estimates on any scale. A total of 237 estimates from 47 studies were included, covering more than 1.5 million cases from various ethnic backgrounds.
Using the Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool, the investigators assessed the study-specific risk of bias; they found that 2, 5, and 40 of the studies had low, moderate, and high risk of bias, respectively. Meta-analysis was conducted using inverse variance-weighted random effects models as the primary approach. According to the investigators, heterogeneity was quantified and adjusted for in a comprehensive bias assessment including several analyses.
Digestive System Cancer Risk
Celiac disease, systemic lupus erythematosus, and type 1 diabetes were found to be positively associated with pancreatic, esophageal, colon, liver, and hepatobiliary cancers. In addition, a positive association was observed between type 1 diabetes and stomach and colorectal cancers. The investigators found that the strongest bias-corrected association was between celiac disease and small intestine cancer (relative risk = 4.19, 95% confidence interval = 2.71–6.50). Multiple sclerosis appeared to be inversely associated with pancreatic, esophageal, rectal, and colorectal cancers.
“The risk of developing cancer of the stomach, esophagus, small intestine, colorectum, hepatobiliary tract, and pancreas in individuals with celiac disease, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes should be further investigated,” the investigators concluded. “If further evidence will confirm these findings, clinical surveillance strategies and personalized cancer screening should be implemented for patients with these autoimmune diseases.”
Additionally, they noted, “Further research is needed to clarify the role of treatment options in patients with the mentioned autoimmune diseases (eg, immunosuppressive therapy, disease-modifying agents) regarding the risk of digestive system cancers.”
The next step, they explained, is to investigate the potential mechanisms responsible for the different associations observed.
Dennis Freuer, MSc, of the University of Augsburg, Germany, is the corresponding author of the article in eClinicalMedicine.
Disclosure: The study was funded by the University of Augsburg. The study authors reported no conflicts of interest.
