Aspirin in the Aetiology of Crohn's Disease and Ulcerative Colitis

A European Prospective Cohort Study

S. S. M. Chan; R. Luben; M. M. Bergmann; H. Boeing; A. Olsen; A. Tjonneland; K. Overvad; R. Kaaks; H. Kennedy; K.-T. Khaw; E. Riboli; A. R. Hart

Disclosures

Aliment Pharmacol Ther. 2011;34(6):649-655. 

In This Article

Methods

A total of 135 780 initially healthy men and women, aged 30–74 years, initially without CD or UC, were recruited into the EPIC cohort Study (European Prospective Investigation into Cancer and Nutrition). Participants were resident in five regions in either: Denmark, Germany or the United Kingdom and were enrolled between the years 1993–1997 (Table 1). Baseline questionnaires were self-completed by participants who supplied information on age, gender, smoking habits and their use of regular aspirin. The term 'regular aspirin' varied between the different recruitment centres and the time periods over which aspirin was recorded ranged between 1 month and 1 year (Table 1). Participants with IBD at recruitment were excluded, as were those diagnosed with inflammatory bowel disease less than 18 months after recruitment. The latter was to ensure that the data accurately reflected aspirin use prior to the development of symptoms, rather than aspirin used as an analgesic for abdominal pain or arthalgia prior to diagnosis. The research protocols were approved by ethic committees in each centre and all subjects gave written informed consent for their data to be used for research.

The cohort was subsequently monitored after recruitment until June 2004 to identify those participants who developed a new diagnosis of either CD or UC. The identification methods used included: local and national inflammatory bowel disease registries, follow-up questionnaires, pathology databases and hospital in-patient records. All the medical notes of potential cases were reviewed by physicians to confirm the diagnoses and to obtain information on both the confirmatory investigations used and the extent of the disease from endoscopic, radiological and surgical records. Participants who developed indeterminate or microscopic colitis were excluded.

In the analysis, each case was matched with four randomly selected controls (from the same centre) for age at recruitment (±6 months), gender and date of recruitment into the study. The control had to be alive on the date of diagnosis of the matched case, to ensure a similar follow-up time to its matched case. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression (STATA statistical package) for CD and UC separately, adjusting for cigarette smoking ('smoker' or 'nonsmoker') at recruitment. Smoking is known to increase the risk of CD but decrease that of UC.[16] Further odds ratios were calculated to investigate any potential interactions between aspirin and smoking. As age, gender and centre were matching variables, these characteristics were not included in the multivariate analysis. The initial analysis included aspirin use data supplied by all countries and a second analysis using only data from Denmark. The latter was done as Denmark recorded aspirin use over the longest time, namely 1 year and had the largest baseline population. The attributable fraction for aspirin use was calculated, namely the portion of CD or UC cases that were associated with regular aspirin use using the formula ((OR-1)/OR) × % cases taking aspirin

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