Review
Intestinal and Extraintestinal Cancers Associated With Inflammatory Bowel Disease

https://doi.org/10.1016/j.clcc.2017.06.009Get rights and content

Abstract

Inflammatory bowel disease (IBD) with its 2 most common entities, ulcerative colitis and Crohn's disease, causes an increased risk of developing intestinal cancers. In fact, malignancies are the second most common cause of death after cardiovascular diseases in both sexes of patients with IBD. Risk factors for colorectal cancer in IBD correlate with the duration of the disease, extent of disease, the association with primary sclerosing cholangitis, family history, and early age at onset. Patients with IBD also have an increased risk for developing a variety of extraintestinal malignancies. In particular, lymphomas, mostly non-Hodgkin lymphomas and skin cancers, are more frequently observed in IBD patients. Longstanding inflammation and the degree of immunosuppression as a result of IBD treatment appear to be the main driving factors for IBD-related carcinogenesis. This review provides an update on the clinical and pathological features of IBD-related intestinal and extraintestinal malignancies.

Introduction

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a lifelong immune-mediated chronic inflammatory disorder of the gastrointestinal tract. Both types of IBD are characterized by chronic inflammation with episodes of remission and relapses.1, 2 It is estimated that at least 0.4% of Europeans and North Americans live with IBD.2 IBD patients are associated with excess deaths from infection, cardiovascular diseases, and cancers.3 Malignancies are the second most common cause of death after cardiovascular diseases in men as well as in women with IBD.4

Inflammatory bowel disease patients are at increased risk of developing carcinoma of the gastrointestinal tract, including colorectal carcinoma and small bowel adenocarcinoma. CD as well as UC carry an increased risk with the greater risk associated with UC. More recently, patients with IBD have also been shown to be at increased risk of developing extraintestinal malignancies, such as lymphomas and skin cancers. This article focuses on the clinical and pathological features of IBD-related intestinal and extraintestinal malignancies.

Section snippets

Inflammatory Bowel Disease-Related Colorectal Cancer

Increased risk of intestinal cancers in IBD patients have been identified in studies of population-based registries, nationwide cohorts, and referral center cohorts.1, 5, 6, 7, 8

A meta-analysis of 116 studies by Eaden et al showed that the prevalence of colorectal cancer in patients with UC is approximately 3.7%.9 The development of cancer accounts for one-third of deaths related to UC. The risk begins to increase significantly above that of the general population approximately 8 to 10 years

Extraintestinal Malignancies Associated With IBD

Early and sustained healing of intestinal inflammation has become the ultimate objective of treatment in IBD. Immunosuppressant therapies, including thiopurines, antitumor necrosis factor, cyclosporine, and methotrexate are frequently necessary for IBD management. Immunosuppressant might be carcinogenic by directly altering cellular DNA, impairing immune control of chronic infection by mutagenic viruses, or reducing immunosurveillance of tumor cells.55, 56, 57 After adjusting for confounders,

Summary

Patients with IBD, including UC and CD, are at increased risk of developing intestinal and extraintestinal cancers. IBD-related malignancies are the second most common cause of death in both sexes of UC and CD patients. The risk for development of intestinal carcinomas in patients with UC and CD appears to depend on the duration of disease, the severity of disease, family history of colorectal cancer, and the presence of PSC. The colorectal cancer risk begins to increase significantly above

Disclosure

The authors have stated that they have no conflicts of interest.

References (73)

  • S. Galandiuk et al.

    Field cancerization in the intestinal epithelium of patients with Crohn's ileocolitis

    Gastroenterology

    (2012)
  • J.X. Yu et al.

    Surveillance of patients with inflammatory bowel disease

    Best Pract Res Clin Gastroenterol

    (2016)
  • F.A. Farraye et al.

    AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease

    Gastroenterology

    (2010)
  • J.A. Leighton et al.

    ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease

    Gastrointest Endosc

    (2006)
  • V. Annese et al.

    European evidence based consensus for endoscopy in inflammatory bowel disease

    J Crohns Colitis

    (2013)
  • J.F. Marion et al.

    Chromoendoscopy is more effective than standard colonoscopy in detecting dysplasia during long-term surveillance of patients with colitis

    Clin Gastroenterol Hepatol

    (2016)
  • T.H. Karlsen et al.

    Update on primary sclerosing cholangitis

    Dig Liver Dis

    (2010)
  • A. Dohan et al.

    Extra-intestinal malignancies in inflammatory bowel diseases: an update with emphasis on MDCT and MR imaging features

    Diagn Interv Imaging

    (2015)
  • L. Beaugerie et al.

    Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study

    Lancet

    (2009)
  • D.S. Kotlyar et al.

    Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis

    Clin Gastroenterol Hepatol

    (2015)
  • D.S. Kotlyar et al.

    A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease

    Clin Gastroenterol Hepatol

    (2011)
  • M.D. Long et al.

    Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease

    Gastroenterology

    (2012)
  • D.K. Podolsky

    Inflammatory bowel disease

    N Engl J Med

    (2002)
  • U. Nieminen et al.

    Malignancies in inflammatory bowel disease

    Scand J Gastroenterol

    (2015)
  • A. Ekbom et al.

    Ulcerative colitis and colorectal cancer: a population-based study

    N Engl J Med

    (1990)
  • C.N. Bernstein et al.

    The epidemiology of inflammatory bowel disease in Canada: a population-based study

    Am J Gastroenterol

    (2006)
  • L. Beaugerie et al.

    Cancers complicating inflammatory bowel disease

    N Engl J Med

    (2015)
  • J.A. Eaden et al.

    The risk of colorectal cancer in ulcerative colitis: a meta analysis

    Gut

    (2001)
  • U. Broomé et al.

    Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer

    Semin Liver Dis

    (2006)
  • M. Rojas-Feria et al.

    Hepatobiliary manifestations in inflammatory bowel disease: the gut, the drugs and the liver

    World J Gastroenterol

    (2013)
  • V. Annese et al.

    European evidence-based consensus: inflammatory bowel disease and malignancies

    J Crohns Colitis

    (2015)
  • K.A. Matkowskyj et al.

    Dysplastic lesions in inflammatory bowel disease: molecular pathogenesis to morphology

    Arch Pathol Lab Med

    (2013)
  • S.H. Itzkowitz et al.

    Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation

    Am J Physiol Gastrointest Liver Physiol

    (2004)
  • L. Hartnett et al.

    Inflammation, DNA methylation and colitis-associated cancer

    Carcinogenesis

    (2012)
  • M. Scarpa et al.

    Inflammatory colonic carcinogenesis: a review on pathogenesis and immunosurveillance mechanisms in ulcerative colitis

    World J Gastroenterol

    (2014)
  • F. Carbonnel et al.

    Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?

    Semin Immunopathol

    (2017)
  • Cited by (36)

    • Tumor cell malignancy: A complex trait built through reciprocal interactions between tumors and tissue-body system

      2022, iScience
      Citation Excerpt :

      These inflammatory conditions are triggered, in part, by gut dysbiosis (Hansen and Sartor, 2015). IBD patients are at increased risk of developing carcinoma of the gastrointestinal tract, including colorectal carcinoma, small bowel adenocarcinoma, but also extra-intestinal malignancies such as lymphomas and skin cancers (Chang et al., 2018). A significant fraction of Crohn’s disease patients develop synchronous and multifocal colorectal carcinoma.

    • Cancer biologics made in plants

      2020, Current Opinion in Biotechnology
      Citation Excerpt :

      We have recently demonstrated that oral administration of a CTB variant (containing a KDEL endoplasmic reticulum retention motif) produced in N. benthamiana can facilitate mucosal healing and reduce tumorigenesis in a colitis-associated colorectal cancer mouse model [53••]. Epidemiological evidence has pointed to an increase in colorectal cancer incidence in inflammatory bowel disease patients [54,55]. Thus, the plant-made CTB variant as a treatment for chronic intestinal inflammation may also have preventive anti-cancer properties that should be investigated further.

    • A comprehensive review and update on ulcerative colitis<sup>,</sup>

      2019, Disease-a-Month
      Citation Excerpt :

      Patients with UC have a higher rate of venous thromboembolic events (deep venous thrombosis and pulmonary embolism) than those without UC, as well as arterial thromboembolic disease such as stroke that may occur at earlier ages; the etiology of this is likely multifactorial.75–79 Finally, patients with UC have an overall increased risk of developing cancers such as colorectal neoplasms and leukemia.80 UC is a chronic disease with variable rates of relapse and remission.

    • Ingested nitrate, disinfection by-products, and risk of colon and rectal cancers in the Iowa Women's Health Study cohort

      2019, Environment International
      Citation Excerpt :

      Colorectal cancer (CRC) is the 3rd most common cancer worldwide and is a major cause of cancer-related death (American Cancer Society (ACS), 2015). Established risk factors include consumption of red and/or processed meats (Domingo and Nadal, 2017, International Agency for Research on Cancer (IARC), 2018) heavy alcohol use, obesity, physical inactivity, a personal history of inflammatory bowel disease, and first-degree family history of CRC (Chang et al., 2018; Wu et al., 2018). Evidence is mixed for specific dietary components, including fiber, certain fats, and consumption of meats cooked at high temperatures (Wu et al., 2018).

    View all citing articles on Scopus
    View full text