Ulcerative colitis and cancer with special reference to the increased colorectal cancer risk

Abstract: The association between ulcerative colitis (UC) and cancer in a defined geographical region in Sweden was analyzed. UC patients have an increased overall risk of cancer of 40%, mainly due not only to the well-known increased risk of colorectal cancer (CRC) but also to the risk of hepatobiliary cancer associated with primary sclerosing cholangitis (PSC). The overall risk is partly counterbalanced by a decreased risk of lung cancer, reflecting the observation that there is a larger proportion of nonand ex- smokers among UC patients than among the general population. A 23-year prospective study to evaluate the safety, reliability, and efficacy of a prospective colonoscopic surveillance program in long-standing UC was analyzed, and estimates of the cumulative risks of developing histologic dysplasia and gross chromosomal abnormalities (DNA aneuploidy) were calculated. A theoretical modified algorithm for separation of low-risk from high-risk cancerprone UC patients early was designed, in order to minimize surveillance efforts and costs. The cumulative risk of having >= low-grade dysplasia at least once after 25 years of disease was 16%, and for DNA aneuploidy it was 29%. Patients with three consecutively negative colonoscopies could be put into a low- risk group in which surveillance could be decreased to colonoscopy every fifth year. Combining histopathology with DNA analyses allows a schedule sufficiently accurate for selection of high-risk patients and also has the potential to reduce the number of colonoscopies by 30%. Colonoscopic surveillance with biopsies for histological assessment and DNA flow cytometry is a reliable and safe way to select high-risk UC patients for prophylactic colectomy. The reproducibility of DNA aneuploidy from one examination to another in a surveillance program for UC was determined, as was the topographical correlation between the aneuploid peaks and histological dysplasia in the colon and rectum. Detection of DNA aneuploidy in UC patients is persistent and reproducible and is closely related to and often precedes histological dysplasia. Widespread aneuploidy indicates that the entire colorectal mucosa is at increased risk of malignant transformation. The relationship between the mucin-associated carbohydrate antigen Sialyl-Tn (STn) and DNA aneuploidy with respect to topographic and temporal distribution in the colon and to areas with dysplasia was analyzed. STn antigen and DNA aneuploidy are independent markers of neoplastic transformation. Determination of STn expression may complement dysplasia and DNA aneuploidy in identifying risk for colonic neoplasia in UC. To analyze the impact of colonoscopic surveillance on CRC mortality in patients with UC, a nested case-control study was performed using observational data from a large population-based cohort of patients with UC. Two out of 40 cases and 18 out of 102 controls had received at least one surveillance colonoscopy [relative risk (RR)=0.29, 95% confidence interval (CI) 0.06-1.31 ]. Twelve of the controls but only one of the cases had been subjected to two or more surveillance colonoscopies (RR=0.22, 95% CI 0.03-1.74), thus indicating a protective dose-response relationship. Colonoscopic surveillance may be associated with a decreased risk of death from colorectal cancer in patients with long- standing ulcerative colitis.