Thiopurines and risk of colorectal neoplasia in patients with inflammatory bowel disease: a meta-analysis

Abstract

Background & aims: Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal neoplasia. Researchers have debated whether treatment of IBD with thiopurines reduces cancer risk. We performed a meta-analysis of thiopurine exposure and risk of colorectal dysplasia or cancer in patients with IBD.

Methods: We used MEDLINE, EMBASE, and Cochrane search engines and abstract books from international conferences to identify relevant literature. We included studies on thiopurine exposure and risk of colorectal neoplasia in patients with ulcerative colitis or Crohn's disease. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) and performed a meta-regression analysis of the effect of year of publication. Various sensitivity analyses were conducted.

Results: Fifteen studies fulfilled the inclusion criteria. Overall, we did not observe a significant effect of thiopurines on risk for colorectal neoplasia (dysplasia and/or cancer) in patients with IBD (OR, 0.87; 95% CI, 0.71-1.06). The estimate did not change markedly in separate assessments of the 2 population-based studies (OR, 0.87; 95% CI, 0.59-1.29), the 13 clinic-based studies (OR, 0.87; 95% CI, 0.59-1.09), the 7 cohort studies (OR, 0.93; 95% CI, 0.67-1.28), or the 8 case-control studies (OR, 0.83; 95% CI, 0.65-1.08). Studies that used neoplasia (dysplasia or cancer) as outcomes tended to show that thiopurines had protective effects (OR for neoplasia, 0.72; 95% CI, 0.50-1.05); these effects were not observed in studies of colorectal cancer (OR, 0.90; 95% CI, 0.72-1.12) or in studies published in recent years (meta-regression; P = .16).

Conclusions: In a meta-analysis, we did not find a significant protective effect of treatment with thiopurines on the risk of colorectal neoplasia in patients with IBD.

Keywords: Azathioprine; Colon Cancer; Inflammation; Risk Factor.