Inflammatory Biomarkers and Colorectal Cancer Risk

结直肠癌（CRC）是美国和许多其他国家癌症死亡的主要原因。 慢性炎症已被认为在CRC的发病机制中起主要作用。我们建议在 本申请在上海妇女健康研究中进行巢式病例对照研究， 一项基于人群的前瞻性队列研究，旨在评估CRC风险与以下几项指标的相关性： 炎症过程的关键产物以及炎症的相关遗传标记。我们特别 将纳入580例CRC事件病例及其单独匹配的对照（生化指标1：1匹配） 标记和1至3个匹配遗传标记）。将测量基线时采集的尿样， 前列腺素E2（PGE 2）的主要代谢产物，采用液相色谱/质谱分析， F2-异前列腺素，使用质谱法。将测量基线血样中的可溶性 肿瘤坏死因子受体、白细胞介素6和C反应蛋白。将测定基因组DNA， 参与PGE 2产生（PTGS 2，PTGES）、代谢（15-PGDH）和 信令（PTGER 1-PTGER 4）。我们将进行统计分析，以评估 这些炎症和CRC风险的生化和遗传标记以及这些标记之间的潜在相互作用 标记。鉴于样本量大，前瞻性研究设计，全面的可用性， 基线调查数据和生物标本，以及良好的合作环境，我们相信， 这项拟议的研究是一个独特的机会，以评估，积极和具有成本效益， 各种炎症标志物与结直肠癌之间的关系。总的来说，这项研究将有助于 这对理解炎症在CRC病因学中的作用以及CRC的发展具有重要意义。 评估CRC风险的新策略。

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.