Skip to main content
SpringerLink
Log in

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis

  • Original Article
  • Published:
Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose/Aim

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC.

Methods

Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I 2 measure of inconsistency. RevMan 5 was utilized for statistical analysis.

Results

Four studies (n = 281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95 % CI: 0.19−1.48, p = 0.23) or colon cancer occurrence (OR 0.50; 95 % CI: 0.18−1.43, p = 0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC.

Conclusion

Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gyde SN, Prior P, Allan RN, et al. Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centers. Gut. 1988;29:206–7.

    Article  PubMed  CAS  Google Scholar 

  2. Lennard-Jones JE. Cancer risk in ulcerative colitis: surveillance or surgery. Br J Surg. 1985;72 Suppl:S84–6.

    Article  PubMed  Google Scholar 

  3. Collins Jr RH, Feldman M, Fordtran JS. Colon cancer, dysplasia, and surveillance in patients with ulcerative colitis. A critical review. N Eng J Med. 1987;316:1654–8.

    Article  Google Scholar 

  4. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med. 1990;323:1228–33.

    Article  PubMed  CAS  Google Scholar 

  5. Sugita A, Sachar DB, Bodian C, Ribeiro MB, Aufses Jr AH, Greenstein AJ. Colorectal cancer in ulcerative colitis. Influence of anatomical extent and age at onset on colitis−cancer interval. Gut. 1991;32:167–9.

    Article  PubMed  CAS  Google Scholar 

  6. Broomé U, Lindberg G, Lofberg R. Primary sclerosing cholangitis in ulcerative colitis—a risk factor for the development of dysplasia and DNA aneuploidy? Gastroenterology. 1992;102:1877–80.

    PubMed  Google Scholar 

  7. Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332:924–33.

    Article  PubMed  CAS  Google Scholar 

  8. Soetikno RM, Lin OS, Heidenreich PA, Young HS, Blackstone MO. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc. 2002;56:48–54.

    Article  PubMed  Google Scholar 

  9. Reddy BS, Wynder EL. Metabolic epidemiology of colon cancer. Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps. Cancer. 1977;39:2533–9.

    Article  PubMed  CAS  Google Scholar 

  10. Moorehead RJ, Campbell GR, Donaldson JD, McKelvey ST. Relationship between duodenal bile acids and colorectal neoplasia. Gut. 1987;28:1454–9.

    Article  PubMed  CAS  Google Scholar 

  11. Morvay K, Szentleleki K, Torok G, Pintér A, Börzsönyi M, Nawroth R. Effect of change of fecal bile acid excretion achieved by operative procedures on 1,2-dimethylhydrazine-induced colon cancer in rats. Dis Colon Rectum. 1989;32:860–3.

    Article  PubMed  CAS  Google Scholar 

  12. Bayerdorffer E, Mannes GA, Richter WO, et al. Increased serum deoxycholic acid levels in men with colorectal adenomas. Gastroenterology. 1993;104:145–51.

    PubMed  CAS  Google Scholar 

  13. Bayerdorffer E, Mannes GA, Ochsenkuhn T, Dirschedl P, Wiebecke B, Paumgartner G. Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. Gut. 1995;36:268–73.

    Article  PubMed  CAS  Google Scholar 

  14. Ochsenkuhn T, Bayerdorffer E, Meining A, et al. Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer. 1999;85:1664–9.

    Article  PubMed  CAS  Google Scholar 

  15. Qiao D, Chen W, Stratagoules ED, Martinez JD. Bile acid-induced activation of activator protein-1 requires both extracellular signal-regulated kinase and protein kinase C signaling. J Biol Chem. 2000;275:15090–8.

    Article  PubMed  CAS  Google Scholar 

  16. Wargovich MJ, Eng VW, Newmark HL, Bruce WR. Calcium ameliorates the toxic effect of deoxycholic acid on colonic epithelium. Carcinogenesis. 1983;4:1205–7.

    Article  PubMed  CAS  Google Scholar 

  17. Bull AW, Marnett LJ, Dawe EJ, Nigro ND. Stimulation of deoxythymidine incorporation in the colon of rats treated intrarectally with bile acids and fats. Carcinogenesis. 1983;4:207–10.

    Article  PubMed  CAS  Google Scholar 

  18. Lapre JA, Termont DS, Groen AK, Van der Meer R. Lytic effects of mixed micelles of fatty acids and bile acids. Am J Physiol. 1992;263:G333–7.

    PubMed  CAS  Google Scholar 

  19. Friedman EA. A multistage model for human colon carcinoma development from tissue culture studies. In: Ingall JRF, Mastromarino AJ, editors. Carcinoma of the large bowel and its precursors. New York: Alan R. Liss, Inc; 1985. p. 175–86.

    Google Scholar 

  20. McMillan L, Butcher S, Wallis Y, Neoptolemos JP, Lord JM. Bile acids reduce the apoptosis-inducing effects of sodium butyrate on human colon adenoma (AA/C1) cells: implications for colon carcinogenesis. Biochem Biophys Res Commun. 2000;273:45–9.

    Article  PubMed  CAS  Google Scholar 

  21. Martinez JD, Stratagoules ED, LaRue JM, et al. Different bile acids exhibit distinct biological effects: the tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation. Nutr Cancer. 1998;31:111–8.

    Article  PubMed  CAS  Google Scholar 

  22. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis–Ursodeoxycholic Acid Study Group. N Engl J Med. 1997;336:691–5.

    Article  PubMed  CAS  Google Scholar 

  23. Narisawa T, Fukaura Y, Terada K, Sekiguchi H. Inhibitory effects of ursodeoxycholic acid on N-methylnitrosourea-induced colon carcinogenesis and colonic mucosal telomerase activity in F344 rats. J Exp Clin Can Res. 1999;18:259–66.

    CAS  Google Scholar 

  24. Narisawa T, Fukaura Y, Terada K, Sekiguchi H. Prevention of N-methylnitrosourea-induced colon tumorigenesis by ursodeoxycholic acid in F344 rats. Jpn J Cancer Res. 1998;89:1009–13.

    Article  PubMed  CAS  Google Scholar 

  25. Earnest DL, Holubec H, Wali RK, et al. Chemoprevention of azomethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid. Cancer Res. 1994;54:5071–4.

    PubMed  CAS  Google Scholar 

  26. Rigas B, Tsioulias GJ, Allan C, Wali RK, Brasitus TA. The effect of bile acids and piroxicam on MHC antigen expression in rat colonocytes during colon cancer development. Immunology. 1994;83:319–23.

    PubMed  CAS  Google Scholar 

  27. Ikegami T, Matsuzaki Y, Shoda J, Kano M, Hirabayashi N, Tanaka N. The chemopreventive role of ursodeoxycholic acid in azoxymethane-treated rats: suppressive effects on enhanced group II phospholipase A2 expression in colonic tissue. Cancer Lett. 1998;134:129–39.

    Article  PubMed  CAS  Google Scholar 

  28. Tung BY, Edmond MJ, Haggitt C, et al. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann Intern Med. 2001;134:89–95.

    PubMed  CAS  Google Scholar 

  29. Pardi DS, Loftus EV, Kremers WK, Keach J, Lindor KD. Ursodeoxycholic acid acts as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology. 2003;124:889–93.

    Article  PubMed  CAS  Google Scholar 

  30. Qiao D, Stratagouleas ED, Martinez JD. Activation and role of mitogen activated protein kinases in deoxycholic acid-induced apoptosis. Carcinogenesis. 2001;22:35–41.

    Article  PubMed  CAS  Google Scholar 

  31. Im E, Martinez JD. Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells. J Nutr. 2004;134:483–6.

    PubMed  CAS  Google Scholar 

  32. Sjöqvist U, Tribukait B, Ost A, Einarsson C, Oxelmark L, Löfberg R. Ursodeoxycholic acid treatment in IBD-patients with colorectal dysplasia and/or DNA-aneuploidy: a prospective, double-blind, randomized controlled pilot study. Anticancer Res. 2004;24:3121–7.

    PubMed  Google Scholar 

  33. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.

    Article  PubMed  CAS  Google Scholar 

  34. Wells GA, Shea B, O’Connell D, et al. The Newcastle−Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  35. Ullman TA, Croog V, Maratchi L, et al. Ursodeoxycholic acid for chemoprevention in ulcerative colitis and primary sclerosing cholangitis: a retrospective cohort study. Am J Gastroenterol. 2003;98:S258.

    Article  Google Scholar 

  36. Wolf JM, Rybicki LA, Lashner BA. The impact of ursodeoxycholic acid on cancer, dysplasia and mortality in ulcerative colitis patients with primary sclerosing cholangitis. Aliment Pharmacol Ther. 2005;22:783–8.

    Article  PubMed  CAS  Google Scholar 

  37. Kornfeld D, Ekbom A, Ihre T. Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary sclerosing cholangitis? A population based study. Gut. 1997;41:522–5.

    Article  PubMed  CAS  Google Scholar 

  38. 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;444:77–85.

    Article  Google Scholar 

  39. Adler DG, Baron TH, Davila RE, et al. ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas. Gastrointest Endosc. 2005;62:1–8.

    Article  PubMed  Google Scholar 

  40. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta analysis. Gut. 2001;48:526–35.

    Article  PubMed  CAS  Google Scholar 

  41. Prior P, Gyde SN, Macartney JC, Waterhouse JA, Allan RN. Cancer morbidity in ulcerative colitis. Gut. 1982;23:490–7.

    Article  PubMed  CAS  Google Scholar 

  42. Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer. 2001;91:854–62.

    Article  PubMed  CAS  Google Scholar 

  43. Itzkowitz SH, Present DH. Crohn’s and Colitis Foundation of American Colon Cancer in IBD Study Group: consensus conference: colorectal cancer screening and surveillance in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11:314–21.

    Article  PubMed  Google Scholar 

Download references

Financial support

None.

Potential competing interests

None.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO, 65212, USA

    Imran Ashraf, Abhishek Choudhary, Murtaza Arif, Michelle L. Matteson, Hazem T. Hammad & Matthew L. Bechtold

  2. OSF MG Gastroenterology, 2805 N. Knoxville Avenue, Peoria, IL, 61604, USA

    Srinivas R. Puli

Authors
  1. Imran Ashraf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abhishek Choudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Murtaza Arif
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle L. Matteson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hazem T. Hammad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Srinivas R. Puli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Matthew L. Bechtold
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew L. Bechtold.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ashraf, I., Choudhary, A., Arif, M. et al. Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis. Indian J Gastroenterol 31, 69–74 (2012). https://doi.org/10.1007/s12664-012-0175-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12664-012-0175-3

Keywords

Search

Navigation