Chemoprevention of colorectal cancer in inflammatory bowel diseases using routinely prescribed medications

Introduction
Colorectal cancer (CRC) is one of the most serious complications of colonic inflammatory bowel diseases. As with any disease, prevention is better than cure and there are several medications used for the condition itself or associated co-morbidity that are potential candidates for the chemoprevention of CRC.

Aims
• To scrutinise the available literature for the potential role of routinely prescribed medications for the chemoprevention of inflammatory bowel disease associated CRC (IBD-CRC).
• To validate the use of the ResearchOne primary care database for use in healthcare research.
• To describe the epidemiology of IBD-CRC cases in the ResearchOne primary care database.
• To assess the role of routinely prescribed medications in the chemoprevention of IBD-CRC within ResearchOne.

Methods
Two systematic reviews and meta-analyses were conducted to assess the role of folate and aspirin or non-aspirin non-steroidal anti-inflammatory agents in the chemoprevention of IBD-CRC. To validate the ResearchOne database, one hundred and forty-seven patients were consented and recruited from hospital IBD clinics and their primary care record was compared with the hospital records. A descriptive analysis was made of the ResearchOne IBD cohort and trends in numbers of IBD-CRC were explored. Finally, a series of nested case control studies were performed to assess the potential role of routinely prescribed medications in preventing CRC in those with IBD. Potential adverse associations with these medications were also explored.

Results
From the limited available evidence, non-aspirin non-steroidal anti-inflammatory medications (NA-NSAID) or aspirin use does not appear to be chemopreventative for CRC in patients with IBD. Following meta-analysis, folate prescription was negatively associated with the development of IBD-CRC (HR 0.58, 95% CI 0.37 to 0.80). Based on the validation study, the ResearchOne database appears a valid resource for healthcare research. These data showed that IBD diagnoses were recorded in 98% of patients, 93% had the correct IBD subtype, and 85% had the first date of diagnosis accurate to within 12 months. In a series of nested case-control studies using the ResearchOne database, 5-ASA medications (OR 0.32, 95% CI 0.23 to 0.45), immunomodulators (OR 0.49, 95% CI 0.31 to 0.79), NA-NSAIDs (OR 0.68, 95% CI 0.49 to 0.95), non-aspirin antiplatelets (OR 0.41, 95% CI 0.20 to 0.84), and statins (OR 0.55, 95% CI 0.37 to 0.81) were negatively associated with IBD-CRC. Statins showed a potential dose association with high dose drugs having a lower odds of IBD-CRC. Statin lipophilicity also was important with lipophilic, but not hydrophilic drugs having a significant association. Being prescribed a statin medication was significantly associated with a reduced number of steroid prescriptions, reduced need for surgical resection one year after diagnosis and reduced odds of being prescribed an immunomodulator medication one year after diagnosis.

Conclusions
CRC remains an important complication of IBD. The routine prescription of 5-ASA drugs, statins or folate supplementation may have a role in the chemoprevention of this disease. Dedicated prospective studies in high-risk groups are now needed. The use of statins may have the additional benefit of controlling disease activity.