Inflammatory Cytokine Gene Polymorphisms, Nonsteroidal Anti-Inflammatory Drug Use, and Risk of Adenoma Polyp Recurrence in the Polyp Prevention Trial

Abstract

Pro- and anti-inflammatory cytokine genes may be important in the maintenance and progression of colorectal cancer. It is possible that single-nucleotide polymorphisms in inflammatory genes may play a role in chronic colonic inflammation and development of colorectal adenomas. Furthermore, common variants in cytokine genes may modify the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colorectal cancer. We examined the association between cytokine gene polymorphisms and risk of recurrent adenomas among 1,723 participants in the Polyp Prevention Trial. We used logistic regression to calculate odds ratios (OR) for the association between genotype, NSAID use, and risk of adenoma recurrence. Cytokine gene polymorphisms were not statistically significantly associated with risk of adenoma recurrence in our study. We observed statistically significant interactions between NSAID use, IL-10 -1082 G>A genotype, and risk of adenoma recurrence (P = 0.01) and multiple adenoma recurrence (P = 0.01). Carriers of the IL-10 -1082 G>A variant allele who were non-NSAID users had a statistically significant decreased risk of multiple adenoma recurrence (OR, 0.43; 95% confidence interval, 0.24-0.77) as well as a nonsignificant 30% decreased risk of any adenoma recurrence. In contrast, NSAID users who were carriers of the IL-10 -1082 G>A variant allele were at an increased risk of any adenoma recurrence (OR, 1.55; 95% confidence interval, 1.00-2.43). These findings suggest that individuals who are carriers of the IL-10 -1082 G>A variant allele may not benefit from the chemoprotective effect of NSAIDs on adenoma polyp recurrence.