Abstract
ObjectiveInflammatory bowel disease (IBD) is commonly treated with thiopurines such as azathioprine and mercaptopurine for the maintenance of remission. Studies examining chemopreventive of these medications on colorectal neoplasm in IBD patients have yielded conflicting results. We performed a meta-analysis to assess the role of thiopurines for this indication.MethodsWe performed a systematic search of PubMed, Web of Science, EMBASE and Cochrane to identify studies reporting colorectal neoplasm from IBD patients treated with thiopurines and conducted a meta-analysis of pooled relative risk (RR) using the random effects model.ResultsNine case-control and ten cohort studies fulfilled the inclusion criteria. The use of thiopurines was associated with a statistically significant decreased incidence of colorectal neoplasm (summary RR=0.71, 95% CI=0.54–0.94, p=0.017), even after adjustment for duration and extent of the disease, but there was high heterogeneity among studies (I 2=68.0%, p<0.001). The RR of advanced neoplasm (high-grade dysplasia and cancer) was 0.72 (95%CI=0.50–1.03, p=0.070) and that of cancer was 0.70 (95% CI=0.46–1.09, p=0.111) for thiopurine-treated patients. Heterogeneity of the studies was affected by the sample size (</≥100 cases) and whether the patients had longstanding colitis (≥7 years).ConclusionThe current meta-analysis revealed that thiopurines had a chemopreventive effect of colorectal neoplasms and a tendency of reducing advanced colorectal neoplasms in IBD. Due to the heterogeneity of included studies, these results should be interpreted with caution.
Highlights
The association of inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been well documented
This study provides a meta-analysis across studies to assess the risk of colorectal neoplasm from IBD on AZA or MP
Our results suggest thiopurine treatment has chemopreventive effect on colorectal neoplasm in IBD patients, and the result remained consistent after adjusting for the extent and duration of the disease
Summary
The association of inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been well documented. A similar CRC risk was observed in Crohn’s colitis based on population-based studies [2]. Thiopurines have been implicated in the development of malignancy due to its immunosuppressive and potential mutagenic effects, especially lymphoma [7] and skin cancers [8]. This often leads to a dilemma as the role of thiopurines in high-risk IBD patients for malignancy [9]. As colorectal dysplasia or cancer is supposed to be the consequence of chronic inflammatory status, chemoprevention of inflammation using AZA/MP could potentially reduce the risk of CRC in patients with IBD. There are no randomized controlled trials and results from observational studies have been mixed
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