Tennessee Colorectal Polyp Study

田纳西州结直肠息肉研究

• 批准号: 8073537
• 负责人: Reid M. Ness
• 金额: $ 40.15万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8073537
• 关键词: Academic Medical Centers; Address; Adenomatous Polyps; Affect; Biological; Biological Assay; Biological Markers; Blood; C-reactive protein; Candidate Disease Gene; Carcinoma; Chemoprevention; Colonoscopy; Colorectal; Colorectal Adenoma; Colorectal Cancer; Colorectal Neoplasms; Colorectal Polyp; Country; Data; Dinoprostone; Epidemiologic Studies; Etiology; Funding; Genes; Genetic Polymorphism; Haplotypes; Hospitals; Hyperplastic Polyp; Incidence; Individual; Inflammation; Lesion; Life Style; Malignant Neoplasms; Measures; Mediator of activation protein; Metabolism; PTGS2 gene; Pathogenesis; Pathology; Pathway interactions; Patients; Phase; Polyps; Premalignant; Principal Investigator; Procedures; Production; Protein C; Protocols documentation; Recruitment Activity; Research; Resources; Reverse Transcriptase Polymerase Chain Reaction; Risk; Risk Assessment; Risk Factors; Sampling; Screening procedure; Serrated Adenoma; Signal Transduction; Slide; TNFRSF5 gene; Tennessee; Testing; Tissues; Tubular Adenoma; United States; Urine; Variant; Veterans; adenoma; base; cancer risk; case control; comparison group; cost; cost effective; follow-up; high risk; mortality; novel; programs; prostaglandin M; response; sample collection; urinary

Colorectal cancer is one of the most common malignancies in the United States and many other countries. Most colorectal cancers arise from adenomatous polyps, pre-malignant lesions that can be removed during an endoscopic procedure to reduce cancer incidence and mortality. Despite considerable research conducted over the past few decades, very few biomarkers have proven useful in assessing individual risk for developing colorectal neoplasia. As part of the renewal for the Tennessee Colorectal Polyp Study (TCPS), we propose to evaluate whether high endogenous production and signaling of prostaglandin E2, a key mediator of COX-2 pathway, may be related to the risk of colorectal adenomas and whether PGE2 -related association may be independent of a low-grade, systematic inflammation, as measured by blood C- reactive protein (CRP). Urinary PGE2 metabolite and blood CRP will be measured in approximately 1000 adenoma patients and polyp-free controls to evaluate the utility of these biomarkers in risk assessment. A two-phase study involving approximately 4600 subjects will be conducted to evaluate polymorphisms in genes affecting PGE2 production (PTGS2, PTGES, 15-PGDH) and signaling (PTGER1-PTGER4) in relation to adenoma risk. Expression levels of genes related to PGE2 production in polyp tissues will be quantified using RT-PCR and correlated with the level of urinary PGE2 metabolite. In addition, we will also investigate risk factors for sessile serrated adenomas (SSA), a group of newly-defined adenomas that may have a different risk profile compared to conventional adenomas. The TCPS is a large, on-going colonoscopy-based epidemiologic study of colorectal adenomas. The resources established in this study will provide exceptional opportunities to test the hypotheses proposed in this application. Results from this study will be valuable for identifying high-risk individuals for cost-effective colorectal screening and chemoprevention.

结直肠癌是美国和许多其他国家最常见的恶性肿瘤之一。 大多数结直肠癌是来自腺瘤息肉，可在 内窥镜检查，以降低癌症的发病率和死亡率。尽管进行了大量研究 在过去的几十年中，很少有生物标志物被证明可用于评估个人风险 用于发展结直肠肿瘤。作为田纳西州结直肠息肉研究的续约一部分 （TCP），我们建议评估前列腺素E2的高内源性产生和信号是否是 COX-2途径的关键介质可能与结直肠腺瘤的风险以及PGE2是否有关 - 相关的关联可能独立于低级，系统的炎症，如血液c-测量 反应蛋白（CRP）。尿液PGE2代谢物和血液CRP将在大约1000中测量 腺瘤患者和无息肉对照，以评估这些生物标志物在风险评估中的效用。一个 将进行涉及大约4600名受试者的两阶段研究以评估多态性 影响PGE2产生（PTGS2，PTGE，15-PGDH）和信号传导（PTGER1-PTGER4）的基因 腺瘤风险。将定量与息肉组织中与PGE2产生有关的基因的表达水平 使用RT-PCR并与尿液PGE2代谢产物的水平相关。此外，我们还将调查 无链锯齿状腺瘤（SSA）的危险因素，这是一组新定义的腺瘤 与常规腺瘤相比，风险特征不同。 TCP是基于结肠镜检查的大型，持续的 大肠腺瘤的流行病学研究。本研究中建立的资源将提供卓越 测试本应用程序中提出的假设的机会。这项研究的结果对于 识别高危个人的结直肠筛查和化学预防。