Patients with inflammatory bowel disease (IBD) have a high risk for colorectal cancer (CRC). This cancer type, which is strongly associated with chronic inflammation, is called colitis-associated CRC (CAC). Understanding the molecular pathogenesis of CAC is crucial to identify biomarkers necessary for early diagnosis and more effective treatment directions. The accumulation of immune cells and inflammatory factors, which constitute a complex chronic inflammatory environment in the intestinal mucosa, may cause oxidative stress or DNA damage to the epithelial cells, leading to CAC development and progression. An important feature of CAC is genetic instability, which includes chromosome instability, microsatellite instability, hypermethylation, and changes in noncoding RNAs. Furthermore, the intestinal microbiota and metabolites have a great impact on IBD and CAC. By clarifying immune, genetic, intestinal microecology, and other related pathogenesis, CAC may be more predictable and treatable.
Keywords: colitis-associated colorectal cancer; genetics; gut microbiota; inflammation; intestinal metabolites.
This review summarizes the molecular pathogenesis of colitis-associated colorectal cancer (CAC) from the aspects of immunity, genetics, and intestinal microecology, and it points out the potential mechanisms worthy of further study. It highlights the complexity of the inflammation process to cancer and the dual effects of inflammatory mediators in order to provide inspiration for finding effective biomarkers or targets to make CAC more predictable and treatable.
© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.