5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study.
OBJECTIVE
The objective of this study was to evaluate the risk of colorectal cancer (CRC) in patients taking aminosalicylates (5-ASA) for inflammatory bowel disease (IBD).


METHODS
The General Practice Research Database (GPRD) which contains the primary care records of five million people in the UK was used to identify users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD. In a nested case control analysis, each incident CRC case with any use of a 5-ASA in the six months before the CRC diagnosis was matched by age, sex, and calendar time to six control patients who were also currently using a 5-ASA. Patients were then classified according to regularity of use. The analysis was controlled for body mass index, IBD duration, history of colorectal polyps, use of non-steroidal anti-inflammatory drugs, paracetamol, aspirin, immunosuppressants, oral and rectal glucocorticoids, prior gastrointestinal hospitalisation, recorded colonoscopy, and number of visits to the general practitioner for IBD symptoms in the 6-24 months before diagnosis.


RESULTS
The study population included 18 969 patients, of whom 100 had developed CRC during 5-ASA exposure. Most of these cases had a history of ulcerative colitis (76 patients). In the case control analysis, regular users, defined as having six or more 5-ASA prescriptions in the previous 12 months, were found to have a decreased risk of CRC compared with irregular users (crude odds ratio (OR) 0.7 (0.44-1.03); adjusted OR 0.60 (0.38-0.96)). Regular users of sulfasalazine with 6-12 prescriptions before had an adjusted OR of 0.95 (0.22-4.11); with 13-30 prior prescriptions this was 0.41 (0.14-1.20) and with >30 prior prescriptions this was 0.77 (0.37-1.60). For mesalazine users, these values were 1.13 (0.49-2.59), 0.30 (0.11-0.83), and 0.31 (0.11-0.84), respectively.


CONCLUSIONS
These results show that regular 5-ASA use is associated with some reduction in the risk of CRC developing in ulcerative colitis.
Division of Epidemiology and Public Health, School of Community Health Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, UK.
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D008875:Middle Aged; D018570:Risk Assessment / Q000379:methods; D014852:Wales / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine