title: Systematic review with meta-analysis: use of 5-aminosalicylates and risk of colorectal neoplasia in patients with inflammatory bowel disease.
abstract: The relationship of 5-aminosalicylates' use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body of research.
  
  
  
  To investigate this association through an updated meta-analysis of observational studies.
  
  
  
  PubMed, Scopus and major conference proceedings were searched up to December 2016. The identified studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates were calculated using random-effect models. Detailed subgroup analyses were performed. The GRADE approach was used to assess the quality of evidence.
  
  
  
  Thirty-one independent observational studies including 2137 cases of colorectal neoplasia (of which 76% were cancers) were incorporated. Between-study heterogeneity was moderate, while strong suspicion of small-study effects was raised. The overall analysis revealed a protective association between 5-aminosalicylates' use and colorectal neoplasia (RR = 0.57, 95% CI: 0.45-0.71). When the analysis was stratified according to study design and setting, the association was significant in cohort (RR = 0.65, 95% CI: 0.43-0.99; n = 10) and case-control studies (RR = 0.53, 95% CI: 0.40-0.70; n = 21), population-based (RR = 0.70, 95% CI: 0.52-0.94; n = 12) and hospital-based studies (RR = 0.46, 95% CI: 0.34-0.61; n = 19). Exposure to 5-aminosalicylates was protective against cancer (RR = 0.58, 95% CI: 0.45-0.74) and dysplasia (RR = 0.54, 95% CI: 0.35-0.84). The reduction in colorectal neoplasia risk was strong in ulcerative colitis (RR = 0.50, 95% CI: 0.38-0.64), but nonsignificant in Crohn's disease (RR = 0.76, 95% CI: 0.43-1.33). Mesalazine (mesalamine) use was protective (RR = 0.70, 95% CI: 0.51-0.94) with evidence of a dose-effect. The effect of sulfasalazine was marginally nonsignificant (RR = 0.72, 95% CI: 0.51-1.01).
  
  
  
  Our findings support a potential chemopreventive role of 5-aminosalicylates in IBD. Further, high-quality prospective research is warranted.
authors.affiliation: IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy.
authors.forename: S
authors.identifier: 0000-0001-6102-6579
authors.initials: S
authors.lastname: Bonovas
authors.affiliation: IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fiorino
authors.affiliation: Hellenic Center for Disease Control and Prevention, Athens, Greece.|Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.|Barcelona Institute for Global Health, Barcelona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Lytras
authors.affiliation: Medical School, University of Cyprus, Nicosia, Cyprus.
authors.forename: G
authors.initials: G
authors.lastname: Nikolopoulos
authors.affiliation: Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France.
authors.forename: L
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy.|Department of Biomedical Sciences, Humanitas University, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Danese
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D003424:Crohn Disease / Q000188:drug therapy*; D006801:Humans; D019804:Mesalamine / Q000627:therapeutic use*; D012306:Risk
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine