Effect of 5-Aminosalicylate Use on Colorectal Cancer and Dysplasia Risk: A Systematic Review and Metaanalysis of Observational Studies

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Abstract
We performed a systematic review with metaanalysis of observational studies evaluating the association between 5-ASA use and colorectal cancer (CRC) or dysplasia among patients with ulcerative colitis. We conducted a search of Medline Embase Biosis, Web of Science, Cochrane Collaboration, manually reviewed the literature, and consulted with experts. Studies were included if they 1) evaluated and clearly defined exposure to 5-aminosalicylates in patients with ulcerative colitis, 2) reported CRC or dysplasia outcomes, 3) reported relative risks or odds ratio or provided data for their calculations. Quantitative analysis using a random-effects model is presented. Nine studies (3 cohort, 6 case–control) containing 334 cases of CRC, 140 cases of dysplasia, and a total of 1,932 subjects satisfied all inclusion criteria. Five studies reported CRC outcomes alone, two studies reported separate cancer and dysplasia outcomes, and two studies reported a combined outcome of CRC or dysplasia. All primary estimates are homogenous. Pooled analysis showed a protective association between use of 5-aminosalicylates and CRC (OR = 0.51; 95% confidence interval (CI): 0.37–0.69) or a combined endpoint of CRC/dysplasia (OR 0.51; 95% CI: 0.38–0.69). 5-ASA use was not associated with a lower risk of dysplasia, although only two studies evaluated this outcome (OR = 1.18; 95% CI: 0.41–3.43). Pooled results of observational studies support a protective association between 5-aminosalicylates and CRC or a combined endpoint of CRC/dysplasia in patients with ulcerative colitis. Additional studies analyzing the effect of 5-ASA on risk of dysplasia are needed.