5-Aminosalicylic Acid and Chemoprevention: Does It Work?
- 1 September 2013
- journal article
- review article
- Published by S. Karger AG in Digestive Diseases
- Vol. 31 (2), 248-253
- https://doi.org/10.1159/000353806
Abstract
5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease (IBD). Intestinal inflammation is the main risk factor for colorectal cancer (CRC) in IBD. Hence, all drugs that are able to induce and maintain mucosal healing (MH) may prevent CRC risk in IBD. In patients with mild to moderate ulcerative colitis (UC), a recent systematic review of 5-ASA trials demonstrated that MH was achieved in nearly 50% of patients. A systematic review including 48 studies linked 5-ASA chemopreventive properties to five distinct pathways: cell cycle progression, scavenging of reactive oxygen- or nitrogen-derived metabolites, TNF-α/TGF-ss signaling, WNT/β-catenin signaling and antibacterial properties. Therefore, in addition to their overall anti-inflammatory activity on the intestinal mucosa, 5-ASA compounds have specific effects on colorectal carcinogenesis at the molecular level. In 2005, a landmark meta-analysis of observational studies found a protective association between 5-ASA and CRC or a combined end point of CRC/dysplasia in UC patients. More recently, a meta-analysis failed to identify a protective effect of 5-ASA on CRC risk in non-referral populations, but in a separate analysis of 9 clinic-based studies, the pooled odds ratio was 0.58 (95% confidence interval: 0.45-0.75), further highlighting the chemopreventive effect of 5-ASA on CRC risk. In conclusion, 5-ASA therapy may reduce CRC risk by healing the mucosa of UC patients and via specific mechanisms of action at the molecular level. Conducting a clinical trial providing the best level of evidence by comparing UC patients receiving 5-ASA treatment versus those included in a placebo arm would be unethical.Keywords
This publication has 41 references indexed in Scilit:
- 255 Aminosalicylates, Thiopurines and the Risk of Colorectal Cancer in Inflammatory Bowel Diseases: A Case-Control Study Nested in the CESAME CohortGastroenterology, 2010
- Systematic review: molecular chemoprevention of colorectal malignancy by mesalazineAlimentary Pharmacology & Therapeutics, 2009
- Mesalamine Protects Against Colorectal Cancer in Inflammatory Bowel DiseaseDigestive Diseases and Sciences, 2009
- Histologic Inflammation Is a Risk Factor for Progression to Colorectal Neoplasia in Ulcerative Colitis: A Cohort StudyGastroenterology, 2007
- 5-ASA Affects Cell Cycle Progression in Colorectal Cells by Reversibly Activating a Replication CheckpointGastroenterology, 2007
- Aminosalicylate Therapy in the Prevention of Dysplasia and Colorectal Cancer in Ulcerative ColitisClinical Gastroenterology and Hepatology, 2006
- Predictive and Protective Factors Associated With Colorectal Cancer in Ulcerative Colitis: A Case-Control StudyGastroenterology, 2006
- Spatial Organization and Composition of the Mucosal Flora in Patients with Inflammatory Bowel DiseaseJournal of Clinical Microbiology, 2005
- Proximal colorectal dysplasia or cancer in ulcerative colitis. The impact of primary sclerosing cholangitis and sulfasalazineDiseases of the Colon & Rectum, 2001
- THE SIGMOIDOSCOPIC PICTURE OF CHRONIC ULCERATIVE COLITIS (NON-SPECIFIC)The American Journal of the Medical Sciences, 1925