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20. Risk factors for inflammatory bowel disease associated colorectal carcinoma

M. Lutgens1, P.D. Siersema1, F. Vleggaar1, M. Broekman1, A.A. van Bodegraven2, G. Dijkstra3, D.W. Hommes4, D. de Jong5, P.C.F. Stokkers6, C.J. van der Woude7, B. Oldenburg1

1University Medical Center Utrecht, Utrecht, The Netherlands; 2VU University Medical Center, Amsterdam, The Netherlands; 3University Medical Center Groningen, Groningen, The Netherlands; 4Leiden University Medical Center, Leiden, The Netherlands; 5Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands; 6Academic Medical Center, Amsterdam, The Netherlands; 7Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

Aim: Inflammatory bowel disease (IBD) patients are at increased risk for colorectal carcinoma (CRC). In order to refine surveillance strategies, it is highly important to identify risk factors for CRC in IBD patients. Therefore the aim of our study was to compare patients diagnosed with IBD-associated CRC with matched controls for baseline variables in a search for risk stratifiers.

Materials and Methods: We designed a retrospective case–control study. All IBD-associated CRC diagnosed between 1990 and 2006 in all tertiary referral centers in the Netherlands were selected via a nationwide pathology database (PALGA). This was also used to indentify controls in a 1:2 ratio matched for our referral population. Follow-up started at January 1st 1990 for all cases and controls. We chose this fixed date to adjust for varying IBD diagnosis dates. All patient variables were collected for that time point. Disease duration up until January 1st 1990 was used as a variable in the multivariate analysis. Multivariate Cox regression analysis was performed to calculate hazard ratios (HR) with 95% confidence intervals (CI). End points were colorectal carcinoma and end of follow-up (proctocolectomy, end of study or lost to follow-up).

Results: A total of 118 IBD-associated colorectal carcinomas were diagnosed after 1990. We identified 206 suitable IBD controls. Mean follow up after January 1st 1990 was 4059 days. Independently associated risk factors for ulcerative colitis were: disease extent >50% of the colon (HR 3.0; 1.4–6.5 95%CI), pseudopolyps (HR 2.5; 1.2–5.2), colonic stenosis (HR 5.2; 2.6–10.3), and 5-ASA medication >3 months (HR 0.4; 0.2–0.8). Independent risk factors for Crohn's disease were disease extent >50% of the colon (HR 4.7; 1.6–14.1) and 5-ASA medication >3 months (HR 0.4; 0.2–0.9). Primary sclerosing cholangitis was associated with an increased hazard ratio but not statistically significant (ulcerative colitis: 1.7; 0.6–4.3, Crohn's: 1.8; 0.2–14.8). Crohn's disease was twice less associated with CRC (HR 0.5; 0.3–0.7).

Conclusion: In the referral center setting extent is an important risk factor for both ulcerative colitis and Crohn's disease. 5-ASA medication is protective in both diseases. Pseudopolyps and colonic stenosis are only associated with CRC in patients with ulcerative colitis.