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  • Review Article
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Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer

Nature Reviews Gastroenterology & Hepatology volume 6, pages 297–305 (2009)Cite this article

Abstract

In patients with IBD, chronic colonic inflammation increases the risk of colorectal cancer, perhaps because inflammation predisposes these tissues to genomic instability. Carcinogenesis in the inflamed colon seems to follow a different sequence of genetic alterations than that observed in sporadic cancers in the uninflamed colon. In this Review, we focus on the genetic alterations in colitis-associated colorectal cancer that contribute to the acquisition of the essential hallmarks of cancer, and on how those alterations differ from sporadic colorectal cancers. Our intent is to provide a conceptual basis for categorizing carcinogenetic molecular abnormalities in IBD, and for understanding how cancer-preventive therapies might target reversal of acquired abnormalities in specific biochemical pathways.

Key Points

  • Chronic colonic inflammation, as occurs in IBD, increases the risk of colorectal cancer, perhaps because inflammation predisposes to genomic instability

  • Carcinogenesis in IBD seems to follow a different sequence of genetic alterations to that observed in sporadic colorectal cancers

  • The molecular alterations that occur in colitis-related carcinogenesis can generally be categorized as endowing cells in the gastrointestinal tract, with one of six hallmarks of cancer cells

  • The essential hallmarks of cancer cells are: proliferation self-sufficiency; resistance to growth-inhibitory signals; avoidance of apoptosis; resisting senescence; belonging to tissues with sustained angiogenesis; and tissue invasion and metastasis

  • An important, emerging concept in colorectal carcinogenesis is that cancers arise from tissue-specific stem cells

  • Understanding the molecular mechanisms of carcinogenesis in IBD-related colorectal cancers will aid in the prevention and treatment of these cancers

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Figure 1: Genetic markers, including upregulation (↑) or downregulation (↓) of gene or protein expression, potentially associated with onset of colitis-associated colorectal carcinoma or of those clinical conditions (chronic inflammation and dysplasia) that progressively lead to the onset of colitis-associated colorectal carcinoma.
Figure 2: Proposed role of inflammation in colitis-associated CRC.

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  1. Dallas Veterans Affairs Medical Center, and University of Texas Southwestern Medical Center, Dallas, TX, USA

    Linda A. Feagins, Rhonda F. Souza & Stuart J. Spechler

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L. A. Feagins declared association with the following company: Centocor, as recipient of grant/research support. RF Souza declared associations with the following companies: AstraZeneca, as consultant and recipient of grant/research support, and TAP Pharmaceutical Products, as consultant. SJ Spechler declared associations with the following companies: AstraZeneca, as consultant and recipient of grant/research support, Takeda, as recipient of grant/research support, and Bârrx Medical as recipient of grant/research support.

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Feagins, L., Souza, R. & Spechler, S. Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer. Nat Rev Gastroenterol Hepatol 6, 297–305 (2009). https://doi.org/10.1038/nrgastro.2009.44

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