Inflammation-Associated Carcinogenesis in Inflammatory Bowel Disease: Clinical Features and Molecular Mechanisms

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD.