Cancer surveillance in inflammatory bowel disease: new molecular approaches.
OBJECTIVE
Patients with chronic inflammatory bowel disease, such as ulcerative colitis and Crohn's disease, have an increased risk of colorectal cancer. Life-long colonoscopy surveillance is performed to detect the presence of dysplasia, but this approach is expensive and time-consuming. Thus, there is intensive research to identify molecular factors with prognostic value. This review summarizes recent research, with a special emphasis on the mechanisms underlying these molecular alterations.


RESULTS
The role of chromosomal instability in the progression to inflammatory bowel disease-associated colorectal cancer is clear and likely relates to chronic cycles of injury, inflammation, repair and telomere shortening. The role of microsatellite instability has been a subject of discussion, and data suggest that microsatellite instability in inflammatory bowel disease might be different from microsatellite instability in sporadic colorectal cancer. Methylation, as a mechanism of gene silencing, also plays a role in ulcerative colitis tumorigenesis. Chronic inflammation has been linked to p53 activation and oxidative stress, contributing to the extensive genomic DNA damage observed in ulcerative colitis.


CONCLUSIONS
Improved understanding of the molecular biology of cancer progression in inflammatory bowel disease will hopefully lead to the identification of useful prognostic biomarkers. Efforts are needed to prove the clinical utility of the most promising markers now identified.
Risques
Rosa Ana
RA
Department of Pathology, University of Washington, USA.
Rabinovitch
Peter S
PS
Brentnall
Teresa A
TA
D014408:Biomarkers, Tumor; D003113:Colonoscopy / Q000379:methods*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications*; D011159:Population Surveillance / Q000379:methods*; D011379:Prognosis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm