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Vol. 31, No. 2, 2013
Issue release date: September 2013

5-Aminosalicylic Acid and Chemoprevention: Does It Work?

Lopez A. · Peyrin-Biroulet L.
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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. © 2013 S. Karger AG, Basel



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References

  1. Crohn BB, Rosenberg H: The sigmoidoscopic picture of chronic ulcerative colitis (non-specific). Am J Med Sci 1925;170:220-228.
  2. Warren S, Sommers SC: Cicatrizing enteritis (regional ileitis) as a pathologic entity. Am J Pathol 1948;24:475-501.

    External Resources

  3. Eaden JA, Abrams KR, Mayberry JF: The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001;48:526-535.
  4. Jess T, Rungoe C, Peyrin-Biroulet L: Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol 2012;10:639-645.
  5. Canavan C, Abrams KR, Mayberry J: Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease. Aliment Pharmacol Ther 2006;23:1097-1104.
  6. Jess T, Gamborg M, Matzen P, Munkholm P, Sorensen TI: Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 2005;100:2724-2729.
  7. Jess T, Simonsen J, Jorgensen KT, Pedersen BV, Nielsen NM, Frisch M: Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology 2012;143:375-381 e1, quiz e13-e14.
  8. Herrinton LJ, Liu L, Levin TR, Allison JE, Lewis JD, Velayos F: Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology 2012;143:382-389.
  9. Itzkowitz SH, Yio X: Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004;287:G7-G17.
  10. Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, et al: Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 2004;126:451-459.
  11. Gupta RB, Harpaz N, Itzkowitz S, Hossain S, Matula S, Kornbluth A, et al: Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 2007;133:1099-1105, quiz 340-341.
  12. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol 2000;95:3452-3457.
  13. Miyoshi J, Yajima T, Shimamura K, Matsuoka K, Okamoto S, Higuchi H, et al: 5-Aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis. Anticancer Res 2012;32:1193-1202.

    External Resources

  14. Baan B, Dihal AA, Hoff E, Bos CL, Voorneveld PW, Koelink PJ, et al: 5-Aminosalicylic acid inhibits cell cycle progression in a phospholipase D dependent manner in colorectal cancer. Gut 2012;61:1708-1715.
  15. Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al: Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut 2004;53:1813-1816.
  16. Romkens TE, Kampschreur MT, Drenth JP, van Oijen MG, de Jong DJ: High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials. Inflamm Bowel Dis 2012;18:2190-2198.
  17. Lyakhovich A, Gasche C: Systematic review: molecular chemoprevention of colorectal malignancy by mesalazine. Aliment Pharmacol Ther 2010;31:202-209.
  18. Luciani MG, Campregher C, Fortune JM, Kunkel TA, Gasche C: 5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint. Gastroenterology 2007;132:221-235.
  19. Munding J, Ziebarth W, Pox CP, Ladigan S, Reiser M, Huppe D, et al: The influence of 5-aminosalicylic acid on the progression of colorectal adenomas via the beta-catenin signaling pathway. Carcinogenesis 2012;33:637-643.
  20. Sun L, Wang X, Yao H, Li W, Son YO, Luo J, et al: Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells. J Environ Pathol Toxicol Oncol 2012;31:95-107.
  21. Campregher C, Luciani MG, Biesenbach P, Evstatiev R, Lyakhovich A, Gasche C: The position of the amino group on the benzene ring is critical for mesalamine's improvement of replication fidelity. Inflamm Bowel Dis 2010;16:576-582.
  22. Swidsinski A, Weber J, Loening-Baucke V, Hale LP, Lochs H: Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol 2005;43:3380-3389.
  23. Subramanian S, Rhodes JM, Hart CA, Tam B, Roberts CL, Smith SL, et al: Characterization of epithelial IL-8 response to inflammatory bowel disease mucosal E. coli and its inhibition by mesalamine. Inflamm Bowel Dis 2008;14:162-175.
  24. Pinczowski D, Ekbom A, Baron J, Yuen J, Adami HO: Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study. Gastroenterology 1994;107:117-120.

    External Resources

  25. Moody GA, Jayanthi V, Probert CS, Mac Kay H, Mayberry JF: Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire. Eur J Gastroenterol Hepatol 1996;8:1179-1183.

    External Resources

  26. Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J: Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther 2000;14:145-153.
  27. Bernstein CN, Blanchard JF, Metge C, Yogendran M: Does the use of 5-aminosalicylates in inflammatory bowel disease prevent the development of colorectal cancer? Am J Gastroenterol 2003;98:2784-2788.
  28. Velayos FS, Terdiman JP, Walsh JM: Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol 2005;100:1345-1353.
  29. Nguyen GC, Gulamhusein A, Bernstein CN: 5-Aminosalicylic acid is not protective against colorectal cancer in inflammatory bowel disease: a meta-analysis of non-referral populations. Am J Gastroenterol 2012;107:1298-1304, quiz 1297, 1305.
  30. Van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, et al: Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohns Colitis 2013;7:1-33.
  31. Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al: Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology 2006;130:1030-1038.
  32. Carrat F SP, Bouvier AM, et al: Aminosalicylates, thiopurines and the risk of colorectal cancer in inflammatory bowel diseases: a case-control study nested in the CESAME cohort. Gastroenterology 2010;138:S-47.
  33. van Schaik FD, van Oijen MG, Smeets HM, van der Heijden GJ, Siersema PD, Oldenburg B: Thiopurines prevent advanced colorectal neoplasia in patients with inflammatory bowel disease. Gut 2012;61:235-240.
  34. Lutgens MW, Siersema PD, Vleggaar FP, et al: Different risk factors for colitis associated colorectal cancer in ulcerative colitis and Crohn's disease. Gastroenterology 2011;140:S-351.
  35. Baars JE, Looman CW, Steyerberg EW, Beukers R, Tan AC, Weusten BL, et al: The risk of inflammatory bowel disease-related colorectal carcinoma is limited: results from a nationwide nested case-control study. Am J Gastroenterol 2011;106:319-328.
  36. Tang J, Sharif O, Pai C, Silverman AL: Mesalamine protects against colorectal cancer in inflammatory bowel disease. Dig Dis Sci 2010;55:1696-1703.
  37. Ullman T, Croog V, Harpaz N, Hossain S, Kornbluth A, Bodian C, et al: Progression to colorectal neoplasia in ulcerative colitis: effect of mesalamine. Clin Gastroenterol Hepatol 2008;6:1225-1230, quiz 177.
  38. Terdiman JP, Steinbuch M, Blumentals WA, Ullman TA, Rubin DT: 5-Aminosalicylic acid therapy and the risk of colorectal cancer among patients with inflammatory bowel disease. Inflamm Bowel Dis 2007;13:367-371.
  39. Jess T, Loftus EV Jr, Velayos FS, Winther KV, Tremaine WJ, Zinsmeister AR, et al: Risk factors for colorectal neoplasia in inflammatory bowel disease: a nested case-control study from Copenhagen county, Denmark and Olmsted county, Minnesota. Am J Gastroenterol 2007;102:829-836.
  40. Rubin DT, LoSavio A, Yadron N, Huo D, Hanauer SB: Aminosalicylate therapy in the prevention of dysplasia and colorectal cancer in ulcerative colitis. Clin Gastroenterol Hepatol 2006;4:1346-1350.
  41. Siegel CA, Sands BE: Risk factors for colorectal cancer in Crohn's colitis: a case-control study. Inflamm Bowel Dis 2006;12:491-496.
  42. van Staa TP, Card T, Logan RF, Leufkens HG: 5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study. Gut 2005;54:1573-1578.
  43. Lindberg BU, Broome U, Persson B: Proximal colorectal dysplasia or cancer in ulcerative colitis. The impact of primary sclerosing cholangitis and sulfasalazine: results from a 20-year surveillance study. Dis Colon Rectum 2001;44:77-85.
  44. Lashner BA, Provencher KS, Seidner DL, Knesebeck A, Brzezinski A: The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 1997;112:29-32.
  45. Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, et al: Second European evidence-based consensus on the diagnosis and management of ulcerative colitis. 2. Current management. J Crohns Colitis 2012;6:991-1030.
  46. Velayos FS, Loftus EV Jr, Jess T, Harmsen WS, Bida J, Zinsmeister AR, et al: Predictive and protective factors associated with colorectal cancer in ulcerative colitis: a case-control study. Gastroenterology 2006;130:1941-1949.


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