OBJECTIVES: Recent studies have implicated primary sclerosing cholangitis (PSC) as a risk factor for colorectal cancer (CRC) in ulcerative colitis (UC). Our study was designed to define both the risk and the risk factors for CRC or dysplasia in a large UC cohort with PSC. METHODS: Patients with UC and PSC were compared with a random sample of UC controls without PSC. Patients were analyzed from the inception of disease until an outcome or censor. RESULTS: Thirty-three (25%) of 132 UC patients with PSC developed CRC or dysplasia compared with 11 (5.6%) of 196 controls (adjusted relative risk 3.15, 95% confidence interval 1.37-7.27). Possible risk factors were chronic disease activity and lack of folate supplementation. Of 17 CRCs in the PSC group, 76% occurred proximal to the splenic flexure and 35% presented at an advanced stage, compared with one of five (20%) CRCs in controls being proximal and none being advanced. Six (4.5%) PSC patients, and no controls, died of CRC (p < 0.01). CONCLUSIONS: UC patients with PSC are at increased risk of developing CRC or dysplasia. Chronically active disease may be a risk factor, whereas folate could have a protective effect. CRCs associated with PSC are more likely to be proximal, to be diagnosed at a more advanced stage, and to be fatal.
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