Inflammatory Biomarkers and Colorectal Cancer Risk

描述（由申请人提供）：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。在本申请中，我们建议在上海妇女健康研究（一项大型基于人群的前瞻性队列研究）中进行巢式病例对照研究，以评估CRC风险与炎症过程中几种关键产物的测量值以及与炎症相关的遗传标记物的相关性。具体而言，我们将纳入580例CRC事件病例及其单独匹配的对照（生化标记1比1匹配，遗传标记1比3匹配）。将使用液相色谱/质谱法测定基线时采集的尿样中前列腺素E2（PGE 2）的主要代谢产物，并使用质谱法测定F2-异前列烷。将测量基线血样的可溶性肿瘤坏死因子-a受体、白细胞介素-6和C反应蛋白。将分析基因组DNA中参与PGE 2产生（PTGS 2、PTGES）、代谢（15-PGDH）和信号传导（PTGER 1-PTGER 4）的基因多态性。我们将进行统计分析，以评估这些炎症的生化和遗传标志物与CRC风险之间的相关性以及这些标志物之间的潜在相互作用。鉴于大样本量，前瞻性研究设计，全面的基线调查数据和生物标本的可用性，以及良好的合作环境，我们认为这项拟议的研究代表了一个独特的机会，以评估，积极和成本效益，炎症和CRC的各种标志物之间的关系。总的来说，这项研究将有助于理解炎症在CRC病因学中的作用，并有助于制定评估CRC风险的新策略。

DESCRIPTION (provided by applicant): 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.