Aspirin, Inflammation Markers, and Colorectal Adenoma

描述(申请人提供)：低剂量阿司匹林已经在几个临床试验中被证明对结直肠腺瘤具有化学预防作用。小剂量阿司匹林发挥抗肿瘤作用的机制存在争议。鉴于慢性炎症与大肠肿瘤的病因有关，而强大的促炎细胞因子可产生原癌效应，因此推测这些细胞因子与大肠肿瘤的病因有关。在这项拟议的研究中，我们将检查促炎症细胞因子/标记物，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，我们还将在没有炎症性疾病或临床异常细胞因子水平的表面上健康的个体中，检查小剂量阿司匹林是否在降低具有致癌潜力的细胞因子水平方面有微妙的效果，以及阿司匹林的化学预防效果是否通过这一机制介导。我们建议在阿司匹林/叶酸息肉预防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，阿司匹林(和叶酸)作为化学预防药物，在1121名有腺瘤病史的患者中预防结直肠腺瘤的复发。患者随机接受安慰剂、81毫克阿司匹林或每天325毫克阿司匹林，并在随访3年后进行终点结肠镜检查。在基线和随访结束时采集血浆样本，测量肿瘤坏死因子-α、白介素6和C反应蛋白水平。本研究将为深入了解大肠肿瘤的病因和小剂量阿司匹林对大肠肿瘤的化学保护机制提供依据。它还可以确定可能从阿司匹林的化学预防中受益最大的目标人群(例如，那些促炎细胞因子水平较高的人群)。

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.