Colitis-Associated Carcinogenesis and Inflammatory Mechanisms

Colitis-associated carcinogenesis arises against a backdrop of chronic intestinal inflammation, most commonly in patients with ulcerative colitis or Crohn’s disease. Persistent mucosal injury and repair promote accumulation of genetic and epigenetic alterations in epithelial cells, driving progression from dysplasia to carcinoma. Central to this process are inflammatory signalling pathways—nuclear factor kappa B (NF-κB), interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3), cyclooxygenase-2 (COX-2)/prostaglandin E₂ and interleukin-23/T helper 17 (Th17)—which collectively foster cell proliferation, inhibit apoptosis and stimulate angiogenesis. Disruption of epithelial barrier integrity allows translocation of microbial products that further activate Toll-like receptors and inflammasomes. Transforming growth factor beta (TGF-β) exhibits context-dependent roles in both restraining and promoting tumour growth, while oxidative stress and reactive nitrogen species inflict DNA damage. The tumour microenvironment is shaped by a dynamic interplay among macrophage subsets, regulatory T cells and other immune effectors, as well as by shifts in gut microbiota composition. Unravelling these interwoven mechanisms has illuminated potential targets for chemoprevention and immunomodulation in colitis-associated cancer.

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Colitis-Associated Carcinogenesis and Inflammatory Mechanisms publication trend

The graph below shows the total number of articles in colitis-associated carcinogenesis and inflammatory mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Colitis-associated cancer (CAC): Colorectal neoplasm arising in the setting of chronic inflammatory bowel disease.

Nuclear factor kappa B (NF-κB): Transcription factor that regulates genes controlling inflammation, cell survival and proliferation.

Signal transducer and activator of transcription 3 (STAT3): Transcriptional regulator activated by cytokines such as IL-6, promoting cell growth and survival.

Transforming growth factor beta (TGF-β): Multifunctional cytokine with dual roles in immune regulation and tumour progression.

Gut microbiota: Diverse community of microorganisms in the intestine influencing inflammation, metabolism and mucosal immunity.

Regulatory T cells (Tregs): Subset of CD4⁺ lymphocytes that suppress excessive immune responses and maintain tolerance.

Th17 cells: CD4⁺ T-cell subset producing interleukin-17, involved in mucosal defence and chronic inflammation.

References

1. The Role of Proinflammatory Pathways in the Pathogenesis of Colitis‐Associated Colorectal Cancer. Mediators of Inflammation (2017).
2. Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis. International Journal of Molecular Sciences (2020).
3. Roles of macrophages on ulcerative colitis and colitis-associated colorectal cancer. Frontiers in Immunology (2023).
4. Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention. Frontiers in Pharmacology (2021).
5. Protective Role of Fecal Microbiota Transplantation on Colitis and Colitis-Associated Colon Cancer in Mice Is Associated With Treg Cells. Frontiers in Microbiology (2019).