From inflammation to carcinogenesis: Distinct pathways and clinical implications of IBD-associated colorectal cancer compared with sporadic CRC

Abstract

Inflammatory bowel disease-associated colorectal cancer (IBD-CRC) represents a distinct clinical and molecular entity compared with sporadic colorectal cancer (CRC). While sporadic CRC arises through the adenoma–carcinoma sequence, IBD-CRC follows an inflammation–dysplasia–carcinoma pathway, characterized by early TP53 alterations, multifocality, and flat lesions that challenge detection. Contemporary epidemiology indicates declining IBD-CRC incidence in high-income regions due to improved surveillance, though risk remains elevated in subgroups with long-standing colitis, primary sclerosing cholangitis (PSC), or persistent inflammation. In contrast, underreporting in low- and middle-income countries obscures the true global burden. Advances in high-definition colonoscopy and chromoendoscopy have improved detection, yet optimal risk-adapted surveillance strategies remain underutilized. Molecular insights highlight differences in genetic alterations, immune evasion, and microbial drivers between IBD-CRC and sporadic CRC. This review synthesizes epidemiologic, pathogenetic, and clinical distinctions, underscores challenges in surveillance and reporting, and discusses emerging technologies—including liquid biopsy, artificial intelligence, and multi-omics—that may refine prevention and early detection. Recognition of IBD-CRC as a separate disease process is essential to optimize individualized risk stratification, surveillance algorithms, and therapeutic strategies.