Aspirin, Inflammation Markers, and Colorectal Adenoma

阿司匹林、炎症标志物和结直肠腺瘤

• 批准号: 6908249
• 负责人: GLORIA YUEN FUN HO
• 金额: $ 27.67万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908249
• 关键词: acute phase protein; adenoma; aspirin; biomarker; cancer prevention; cancer risk; clinical research; colorectal neoplasms; human data; human therapy evaluation; human tissue; inflammation; interleukin 6; neoplasm /cancer chemotherapy; pharmacokinetics; protein metabolism; relapse /recurrence; tumor necrosis factor alpha

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.

描述（由申请人提供）：几项临床试验显示，低剂量阿司匹林对结直肠腺瘤具有化学预防作用。低剂量阿司匹林发挥其抗肿瘤作用的机制是有争议的。鉴于慢性炎症与结直肠肿瘤的病因有关，并且强效促炎细胞因子可具有促癌作用，因此假设这些细胞因子与结直肠肿瘤的病因相关。在这项研究中，我们将检查促炎细胞因子/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，在没有炎性疾病或临床异常水平的细胞因子，低剂量阿司匹林是否有一个微妙的影响，降低细胞因子的致癌潜力，以及是否阿司匹林的化学预防疗效介导的，通过这种机制。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，在1，121例有腺瘤病史的患者中研究阿司匹林（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、81 mg阿司匹林组或每日325 mg阿司匹林组，并在随访3年后进行终点结肠镜检查。将测量基线和随访结束时获得的血浆样本的TNF-α、IL-6和CRP水平。本研究将有助于深入了解结直肠肿瘤的病因学和低剂量阿司匹林在结直肠肿瘤中的化学保护机制。它还可以识别目标人群（例如，那些具有高水平促炎细胞因子的人），他们可能从阿司匹林的化学预防中获益最多。