Colorectal cancer in ulcerative colitis: unraveling mechanisms and advancing surveillance and chemoprevention

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer through inflammation-driven carcinogenesis distinct from sporadic disease. Although the relative risk remains elevated, contemporary population-based studies indicate a substantial decline in absolute incidence, likely reflecting improved disease control, biologic therapies and structured surveillance colonoscopy. This review synthesizes current evidence on the epidemiology and determinants of colitis-associated colorectal cancer (CAC), highlighting key risk modifiers such as disease extent and duration, persistent inflammation, family history, and primary sclerosing cholangitis. We further summarize advances in understanding the molecular and immunologic mechanisms underlying CAC, including genomic instability, immune dysregulation, oxidative stress, microbiome alterations, and tumor microenvironment remodeling. Emerging molecular and histologic biomarkers that may enhance risk stratification and guide precision surveillance are discussed. In addition, contemporary surveillance approaches and evolving chemoprevention strategies are critically evaluated. Collectively, this review outlines current challenges and future directions for individualized CRC prevention in patients with UC.