Dysplasia and colorectal cancer in inflammatory bowel disease: a result of inflammation or an intrinsic risk?

Patients with inflammatory bowel disease (IBD) face an increased lifetime risk of developing colorectal cancer (CRC). Although CRC in IBD only accounts for 1-2% of all cases of CRC in the general population, it is responsible for approximately 15% of the mortality of patients with Crohn's disease (CD) and ulcerative colitis (UC). Independent factors associated with increased risk include long disease duration, extensive colonic involvement, young age at onset of IBD, severity of inflammation, primary sclerosing cholangitis, backwash ileitis and a family history of CRC. Many of these factors emphasise the role of inflammation as an underlying mechanism. Despite the differences between the molecular abnormalities found in colitis-associated dysplasia in comparison with sporadic CRC, IBD-associated cancer has a similar dysplasia-cancer sequence, similar frequencies of major chromosomal abnormalities, microsatellite instability and similar glycosylation changes. These similarities seem to outweigh the differences and make it reasonable to suggest that not only IBD-associated CRC but even sporadic colon cancer might be largely secondary to inflammation. Oxidative stress, apoptosis, COX-2 activity and a possible common inherited defective glycosylation are thought to play a key role in the pathogenesis of colitis-associated CRC. DNA alterations initiated in colonic crypts can expand to adjacent crypts through crypt fission. There seems little doubt that the increased risk of cancer in inflammatory bowel diseases is a result of the disease rather than an inherited phenomenon. An understanding of the definition and pathogenesis of CRC in IBD is crucial to optimise patient management. Further investigation is therefore necessary.