Inflammatory Biomarkers and Colorectal Cancer Risk

在美国和许多其他国家，结直肠癌(CRC)是癌症死亡的主要原因。 慢性炎症被认为在结直肠癌的发病机制中起主要作用。我们建议在 这一应用程序在上海妇女健康研究中进行嵌套病例对照研究，一个大型 基于人群的前瞻性队列研究，以评估结直肠癌风险与以下几项措施的相关性 炎症过程的关键产物以及与炎症相关的遗传标记。具体来说，我们 将包括580例结直肠癌病例及其各自匹配的对照(1比1匹配生化 标记和1到3个匹配的遗传标记)。在基线上采集的尿样将被测量 前列腺素E_2(PGE_2)主要代谢物的液-质联用分析 F2-异前列腺素的质谱学研究。将测量基线血样中的可溶物 肿瘤坏死因子-a受体、白介素6和C反应蛋白。将对基因组DNA进行检测 与前列腺素E_2的产生(Ptgs2，PtGES)、代谢(15-PGDH)有关的基因的多态性，以及 信令(PTGER1-PTGER4)。我们将进行统计分析以评估两者之间的关联 这些炎症和结直肠癌风险的生化和遗传标记物及其潜在的相互作用 记号笔。考虑到大样本量、前瞻性研究设计、可获得性 基线调查数据和生物群落，以及良好的协作环境，我们相信 这项拟议的研究是一个独特的机会，可以积极和具有成本效益地评估 多种炎症标志物与结直肠癌的关系总的来说，这项研究将有助于 对了解炎症在结直肠癌发病机制中的作用及其发生发展具有重要意义 评估儿童权利公约风险的新战略。

Colorectal cancer (CRC) is a major cause of cancer deaths in the United States and many other countries. Chronic inflammation has been suggested to play a major role in the pathogenesis of CRC. We propose in this application to conduct a nested case-control study within the Shanghai Women's Health Study, a large population-based prospective cohort study, to evaluate the association of CRC risk with measures of several key products of the inflammatory process and with related genetic markers of inflammation. Specifically, we will include 580 incident cases of CRC and their individually matched controls (1 to1 match for biochemical markers and 1 to 3 match for genetic markers). Urine samples collected at baseline will be measured for a major metabolite of prostaglandin E2 (PGE2) using a liquid chromatographic/mass spectrometric assay and F2-isoprostanes using the mass spectrometric method. Baseline blood samples will be measured for soluble tumor necrosis factor-a receptors, interleukin-6, and C-reactive protein. Genomic DNA will be assayed for polymorphisms in genes involved in PGE2 production (PTGS2, PTGES), metabolism (15-PGDH), and signaling (PTGER1-PTGER4). We will perform statistical analyses to evaluate the associations between these biochemical and genetic markers of inflammation and CRC risk and potential interactions of these markers. Given the large sample size, the prospective study design, the availability of comprehensive baseline survey data and biospecimens, as well as the excellent collaborative environment, we believe that this proposed study represents a unique opportunity to evaluate, vigorously and cost-efficiently, the relationship between various markers of inflammation and CRC. Overall, this study will contribute significantly to the understanding of the role of inflammation in the etiology of CRC and to the development of new strategies for the assessment of CRC risk.