Risk of Cancer in Inflammatory Bowel Disease Treated With Azathioprine: A UK Population-Based Case-Control Study

OBJECTIVES: Azathioprine is an accepted treatment of inflammatory bowel disease (IBD), but concerns exist regarding its carcinogenic potential. Studies in renal transplant and rheumatology patients have reported an increased cancer risk. In IBD, studies suggest a small increased risk of lymphoma and protection against colorectal cancer, but the overall risk of malignancy has not been established. METHODS: We conducted a nested case-control study using the General Practice Research Database. Records of IBD patients were examined for azathioprine prescriptions and cancers. Prescriptions per year of follow-up were grouped for analysis. Azathioprine use was compared between IBD cases (with a diagnosed cancer) and IBD controls (without). RESULTS: Overall, 15,471 patients with IBD and over 1 year of appropriate data were identified. Among these, 392 developed cancer, of whom 10.5% received at least one prescription for azathioprine, compared with 1,914 (12.7%) of the controls. Analyzing the occurrence of any cancer against azathioprine prescription showed a nonsignificant protective effect (odds ratio (OR) =0.92, 95% confidence interval (CI) = 0.79-1.06). Correction for the effects of age and smoking removed this effect (OR = 1.04, 95% CI = 0.89-1.21). Diagnosis of lymphoma was associated with ever use of azathioprine with OR of 3.22, CI = 1.01-10.18. CONCLUSIONS: We found evidence of an increased risk of lymphoma, which is consistent with previous studies. We found no overall increase in risk of cancer in individuals with IBD who had taken azathioprine. Our study does not show a need for azathioprine cessation in the medium term in IBD because of the risk of malignancy.