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The Risk of Colorectal Cancer in Patients with Ulcerative Colitis

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Abstract

Background and Aim

Ulcerative colitis increases the risk of developing dysplasia and colitis-associated cancer (CAC). The purpose of this study was to determine the risk factors as well as protective measures for disease burden, need for colectomy and the development of CAC in ulcerative colitis (UC) patients.

Methods

A cohort of n = 434 UC patients was evaluated. Data analysis was performed by univariate and multivariate logistic regression. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated, and significance was assessed by the likelihood ratio test.

Results

Mean patient age at UC diagnosis was 45.7 ± 15.1 years which manifested mainly as pancolitis (47 %) or left-sided colitis (45.2 %). CAC was detected in ten patients (2.3 %). UC disease duration was strongly associated with the risk of CAC (P < 0.0014); disease duration between 9 and 15 years: OR of 2.5 (95 % CI 0.2–41.1), more than 15 years: OR of 21.4 (95 % CI 2.6–173.6). The risk of developing dysplasia (low-grade intraepithelial neoplasia, LGIEN and high-grade intraepithelial neoplasia, HGIEN) or the need to undergo colectomy was also significantly related to disease duration (P = 0.006, P = 0.002, respectively). Established anti-inflammatory medication (e.g., 5-ASA, anti-TNF-α) significantly reduced the risk of both dysplasia and CAC (P = 0.02).

Conclusions

Despite the use of modern therapies for UC, CAC rates remain high. In our study, risk factors included disease duration while anti-inflammatory therapies reduced the risk. Effective control of the intestinal inflammation also reduced the disease burden as indicated by decreased risk of requiring colectomy, underscoring the need for sufficient surveillance and anti-inflammatory therapies.

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References

  1. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–899.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med. 1990;323:1228–1233.

    Article  CAS  PubMed  Google Scholar 

  3. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement. Lancet. 1990;336:357–359.

    Article  CAS  PubMed  Google Scholar 

  4. Choi PM, Zelig MP. Similarity of colorectal cancer in Crohn’s disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut. 1994;35:950–954.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Eddy DM. Screening for colorectal cancer. Ann Intern Med. 1990;113:373–384.

    Article  CAS  PubMed  Google Scholar 

  6. Munkholm P. Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease. Alim Pharmacol Ther. 2003;18:1–5.

    Article  Google Scholar 

  7. Claessen MM, Lutgens MW, van Buuren HR, et al. More right-sided IBD-associated colorectal cancer in patients with primary sclerosing cholangitis. Inflamm Bowel Dis. 2009;15:1331–1336.

    Article  CAS  PubMed  Google Scholar 

  8. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–535.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451–459.

    Article  PubMed  Google Scholar 

  10. 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 

  11. Askling J, Dickman PW, Karlen P, et al. Family history as a risk factor for colorectal cancer in inflammatory bowel disease. Gastroenterology. 2001;120:1356–1362.

    Article  CAS  PubMed  Google Scholar 

  12. Devroede GJ, Taylor WF, Sauer WG, Jackman RJ, Stickler GB. Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med. 1971;285:17–21.

    Article  CAS  PubMed  Google Scholar 

  13. 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 e371; quiz e313-374.

  14. Winther KV, Jess T, Langholz E, Munkholm P, Binder V. Long-term risk of cancer in ulcerative colitis: a population-based cohort study from Copenhagen County. Clin Gastroenterol Hepatol. 2004;2:1088–1095.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. Choi PM, Nugent FW, Schoetz DJ Jr, Silverman ML, Haggitt RC. Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis. Gastroenterology. 1993;105:418–424.

    CAS  PubMed  Google Scholar 

  17. Vleggaar FP, Lutgens MW, Claessen MM. Review article: The relevance of surveillance endoscopy in long-lasting inflammatory bowel disease. Alim Pharmacol Ther. 2007;26:47–52.

    Article  Google Scholar 

  18. Farraye FA, Odze RD, Eaden J, et al. AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology. 2010;138:738–745.

    Article  PubMed  Google Scholar 

  19. Jess T, Gamborg M, Munkholm P, Sorensen TI. Overall and cause-specific mortality in ulcerative colitis: meta-analysis of population-based inception cohort studies. Am J Gastroenterol. 2007;102:609–617.

    Article  PubMed  Google Scholar 

  20. Lutgens MW, Vleggaar FP, Schipper ME, et al. High frequency of early colorectal cancer in inflammatory bowel disease. Gut. 2008;57:1246–1251.

    Article  CAS  PubMed  Google Scholar 

  21. Vienne A, Simon T, Cosnes J, et al. Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort. Alim Pharmacol Ther. 2011;34:188–195.

    Article  CAS  Google Scholar 

  22. Subramaniam K, Richardson A, Dodd J, Platten J, Shadbolt B, Pavli P. Early predictors of colectomy and long-term maintenance of remission in ulcerative colitis patients treated using anti-TNF therapy Intern Med J 2014.

  23. Satsangi J, Silverberg MS, Vermeire S, Colombel JF, Satsangi J. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–753.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–1629.

    Article  CAS  PubMed  Google Scholar 

  25. Riddell RH, Goldman H, Ransohoff DF, et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol. 1983;14:931–968.

    Article  CAS  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. Lutgens MW, van Oijen MG, van der Heijden GJ, Vleggaar FP, Siersema PD, Oldenburg B. Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis. 2013;19:789–799.

    Article  PubMed  Google Scholar 

  28. Moore SE, McGrail KM, Peterson S, et al. Infliximab in ulcerative colitis: the impact of preoperative treatment on rates of colectomy and prescribing practices in the province of British Columbia, Canada. Dis Colon Rectum. 2014;57:83–90.

    Article  PubMed  Google Scholar 

  29. Rutter MD, Saunders BP, Wilkinson KH, et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology. 2006;130:1030–1038.

    Article  PubMed  Google Scholar 

  30. Cravo ML, Albuquerque CM, Salazar de Sousa L, et al. Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation. Am J Gastroenterol. 1998;93:2060–2064.

    Article  CAS  PubMed  Google Scholar 

  31. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–434.

    Article  CAS  PubMed  Google Scholar 

  32. Rubin DT, Huo D, Kinnucan JA et al. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study Clin Gastroenterol Hepatol. 2013;11:1601–1608 e1601–1604.

  33. Lukas M. Inflammatory bowel disease as a risk factor for colorectal cancer. Dig Dis. 2010;28:619–624.

    Article  PubMed  Google Scholar 

  34. Jess T, Loftus EV, Velayos FS Jr, 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.

    Article  PubMed  Google Scholar 

  35. Ullman T, Croog V, Harpaz N et al. Progression to colorectal neoplasia in ulcerative colitis: effect of mesalamine. Clin Gastroenterol Hepatol. 2008;6:1225–1230; quiz 1177.

  36. Bernstein CN, Nugent Z, Blanchard JF. 5-Aminosalicylate is not chemoprophylactic for colorectal cancer in IBD: a population based study. Am J Gastroenterol. 2011;106:731–736.

    Article  CAS  PubMed  Google Scholar 

  37. Ali RA, Egan LJ. How to manage the risk of colorectal cancer in ulcerative colitis. Curr Drug Targets. 2011;12:1424–1432.

    Article  CAS  PubMed  Google Scholar 

  38. Herfarth H. The role of chemoprevention of colorectal cancer with 5-aminosalicylates in ulcerative colitis. Dig Dis. 2012;30:55–59.

    Article  PubMed  Google Scholar 

  39. Biancone L, Michetti P, Travis S, et al. European evidence-based Consensus on the management of ulcerative colitis: special situations. J Crohns Colitis. 2008;2:63–92.

    Article  PubMed  Google Scholar 

  40. Dignass A, Preiss JC, Aust DE, et al. [Updated German guideline on diagnosis and treatment of ulcerative colitis, 2011]. Z Gastroenterol. 2011;49:1276–1341.

    Article  CAS  PubMed  Google Scholar 

  41. Hoffmann JC, Zeitz M, Bischoff SC, et al. [Diagnosis and therapy of ulcerative colitis: results of an evidence based consensus conference by the German society of digestive and metabolic diseases and the competence network on inflammatory bowel disease]. Z Gastroenterol. 2004;42:979–983.

    Article  CAS  PubMed  Google Scholar 

  42. Neurath MF, Travis SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut. 2012;61:1619–1635.

    Article  CAS  PubMed  Google Scholar 

  43. Velayos FS, Loftus EV Jr, Jess T, et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: a case-control study. Gastroenterology. 2006;130:1941–1949.

    Article  PubMed  Google Scholar 

  44. Soderlund S, Granath F, Brostrom O, et al. Inflammatory bowel disease confers a lower risk of colorectal cancer to females than to males. Gastroenterology. 2010;138:1697–1703.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Faekah Gohar for proofreading the manuscript. D. Bettenworth was supported by a research fellowship from the Faculty of Medicine, Westfälische Wilhelms-Universität Münster. M. Brückner was supported by a “Gerok” rotational position of the Deutsche Forschungsgemeinschaft (DFG SFB1009B8).

Conflict of interest

There was no financial support for this study, and the authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine B, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany

    Tobias M. Nowacki, Markus Brückner, Phil Tepasse, Friederike Pott, Karin Hengst & Dominik Bettenworth

  2. Institute of Biostatistics and Clinical Research, University Münster, Münster, Germany

    Maria Eveslage

  3. Department of Hematology and Oncology, Hubertus Wald Tumorzentrum, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Nils H. Thoennissen

  4. Christophorus-Kliniken GmbH, St.-Vincenz-Hospital Coesfeld, Coesfeld, Germany

    Matthias Ross

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  1. Tobias M. Nowacki
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Correspondence to Dominik Bettenworth.

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Tobias M. Nowacki, Markus Brückner, Matthias Ross and Dominik Bettenworth have contributed equally to this work.

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Nowacki, T.M., Brückner, M., Eveslage, M. et al. The Risk of Colorectal Cancer in Patients with Ulcerative Colitis. Dig Dis Sci 60, 492–501 (2015). https://doi.org/10.1007/s10620-014-3373-2

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  • DOI: https://doi.org/10.1007/s10620-014-3373-2

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