Cancer Prevention Program
Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) reduces the incidence of colon adenomas as well as carcinomas by approximately 50%. Enzymes prominently involved in metabolizing aspirin are UDP-glucuronsyltransferases (UGT). UGT1A6 is a polymorphic UGT and its variant alleles metabolize aspirin less efficiently. In NSAIDs users, and aspirin users in particular, the risk of colon neoplasia is reduced only in individuals who are UGT1A6 heterozygous and homozygous variant, but not homozygous wild-type. Aspirin and its metabolite, salicylic acid, can inhibit growth through the inhibition of cyclooxygenases (catalysts of prostaglandin synthesis), the promotion of apoptosis, and other as yet unidentified pathways. The goal of this project is to determine the affect of UGT1A6 genotype on aspirin metabolism and on aspirin-induced changes in the colonic gene expression and protein markers of apoptosis (BAX and Bcl-2).
This is a two tiered study, first a cross-sectional design identified UGT1A6 type in 400+ participants between 21 and 45 years of age recruited from the community. Once UGT1A6 is known, persons with specific genotypes were invited to participate in the aspirin intervention trial – a crossover double blinded design where placebo or aspirin (325 mg) were taken 60 days with a 3-month washout period between each treatment period and sigmoidoscopy with biopsies at the end of each period. Recruitment has been completed for this study.
Contact: Lisa Levy.