Aspirin, Inflammation Markers, and Colorectal Adenoma

描述（由申请人提供）：在一些临床试验中显示，低剂量阿司匹林对结直肠腺瘤具有化学预防作用。小剂量阿司匹林发挥其抗肿瘤作用的机制存在争议。鉴于慢性炎症与结直肠肿瘤的病因有关，而强效的促炎细胞因子可能具有促癌作用，我们假设这些细胞因子与结直肠肿瘤的病因有关。在这项拟议的研究中，我们将研究促炎细胞因子/标志物，即肿瘤坏死因子- α (tnf - α)， IL-6和C反应蛋白（CRP）是否与结直肠腺瘤的风险相关。此外，我们将研究，在没有炎症性疾病或临床细胞因子水平异常的表面健康个体中，低剂量阿司匹林是否对降低具有致癌潜力的细胞因子水平有微妙的作用，以及阿司匹林的化学预防功效是否通过这一机制介导。我们建议在阿司匹林/叶酸预防息肉研究中进行一项辅助研究，这是一项随机、双盲、安慰剂对照试验，在1121例有腺瘤病史的患者中，阿司匹林（和叶酸）作为化学预防剂预防结直肠腺瘤复发。患者被随机分配到安慰剂组、每天服用81毫克阿司匹林组或325毫克阿司匹林组，并在3年随访后进行结肠镜检查。基线和随访结束时获得的血浆样本将被测量tnf - α、IL-6和CRP的水平。本研究将为结直肠肿瘤的病因学和小剂量阿司匹林对结直肠肿瘤的化学保护机制提供新的见解。它还可以确定目标人群（例如，那些具有高水平的促炎细胞因子的人群），他们可能从阿司匹林的化学预防中获益最多。

DESCRIPTION (provided by applicant): 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.