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The continuing uncertainty about cancer risk in inflammatory bowel disease
  1. Hans-Olov Adami1,
  2. Michael Bretthauer2,
  3. Louise Emilsson2,
  4. Miguel A Hernán3,
  5. Mette Kalager2,
  6. Jonas F Ludvigsson4,
  7. Anders Ekbom5
  1. 1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  2. 2Institute of Health and Society, University of Oslo, Oslo, Norway
  3. 3Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  4. 4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  5. 5Department of Medicine Solna, Clinical Epidemiology Unit T2, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Professor Hans-Olov Adami, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave., Boston MA 02115, USA; hadami{at}

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An increased risk of colorectal cancer (CRC) among individuals with IBD was suggested in the 1920s and later supported by epidemiologic studies.1 The association between IBD and CRC is not thought to arise from shared risk factors,2 but rather from a causal effect of IBD on CRC through chronic inflammation and other mechanisms that promote malignant transformation of the colonic mucosa.3 As a result, patients with IBD are considered at high risk of CRC and therefore receive anti-inflammatory treatment, colonoscopic surveillance with biopsies and prophylactic colectomy.

Multiple reviews and meta-analyses have tried to estimate CRC risk in patients with IBD (see table 1 for a summary from six such analyses4–9) and several additional studies were published during the last year.10–13 Few of these studies are large, prospective, population-based studies, which reflect the substantial methodological challenges. Here, we first outline the criteria for valid studies on IBD and cancer and then use those criteria to critically review the existing studies.

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Table 1

Summary of meta-analyses of the association between IBD, UC and Crohn's disease (CD) and risk of colorectal cancer (CRC)

Methodological challenges

Defining disease onset

Failure to accurately ascertain the onset of IBD may bias the effect estimates of IBD on cancer if increasing duration of disease increases the probability of somatic mutations that lead to malignant transformation. However, IBD may only be detected years after onset during colonoscopy screening14 or after early symptoms of CRC. As a result, the relative risk of CRC may be overestimated. Unfortunately, the identification of IBD onset in existing population-based registers is challenging. Its replacement by first hospitalisation due to IBD may misclassify disease onset because outpatient management may suffice until exacerbations, surgical treatment or complications require inpatient care.

A better choice for an operational definition of disease onset would be the date of first …

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  • Contributors H-OA wrote the first draft of this manuscript and AE has resumed main responsibility for the literature review. Subsequently, all authors have been deeply involved in discussions and several rounds of editing of the manuscript to an extent that, beyond any doubt, justifies authorship. All authors have approved the current version.

  • Funding Karolinska Institutet Distinguished Professor Award to H-OA (Dnr: 2368/10-221), NIH grant P01 CA134294.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.