Low-dose aspirin has been shown in several clinical trials to exert a chemopreventive effect on colorectal adenomas. The mechanism by which low-dose aspirin exerts its anti-neoplastic effects is controversial. Given that chronic inflammation is implicated in the etiology of colorectal neoplasia, and potent proinflammatory cytokines can have prooncogenic effects, it is hypothesized that these cytokines are associated with the etiology of colorectal neoplasia. In this proposed study, we will examine if proinflammatory cytokines/marker, namely tumor necrosis factor-alpha (TNF-alpha), IL-6, and C reactive protein (CRP), are associated with the risk of colorectal adenoma. In addition, we will examine, in apparently healthy individuals without inflammatory disease or clinically abnormal levels of cytokines, whether lowdose aspirin has a subtle effect on reducing the levels of cytokines with oncogenic potential, and whether the chemopreventive efficacy of aspirin is mediated through this mechanism. We propose an ancillary study in the Aspirin/Folate Polyp Prevention Study, a randomized, double blind, placebo-controlled trial of aspirin (and folate) as a chemopreventive agent against recurrence of colorectal adenomas in 1,121 patients with a history of adenomas. Patients were randomized to placebo, 81 mg of aspirin, or 325 mg of aspirin daily, and an endpoint colonoscopy was conducted after 3 years of follow-up. Plasma samples obtained at baseline and the end of follow-up will be measured for levels of TNF-alpha, IL-6, and CRP. This study will provide insight into the etiology of colorectal neoplasia and the chemoprotective mechanism of low-dose aspirin in colorectal neoplasia. It may also identify target populations (e.g., those with high levels of proinflammatory cytokines) who may benefit most from chemoprevention of aspirin.
| Wang, Tao; Ho, Gloria; Ye, Kenny et al. (2009) A partial least-square approach for modeling gene-gene and gene-environment interactions when multiple markers are genotyped. Genet Epidemiol 33:6-15 |
| Ho, Gloria Y F; Xue, Xiaonan; Cushman, Mary et al. (2009) Antagonistic effects of aspirin and folic acid on inflammation markers and subsequent risk of recurrent colorectal adenomas. J Natl Cancer Inst 101:1650-4 |
