Barrett's Esophagus: Predictors of Progression

巴雷特食管：进展的预测因素

• 批准号: 7893223
• 负责人: BRIAN J REID
• 金额: $ 245.71万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-16 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7893223
• 关键词: Barrett; Esophagus; Predictors; Progression

DESCRIPTION (provided by applicant): This P01 renewal application comes from an experienced research team that will investigate Barrett's esophagus (BE), the only established precursor to esophageal adenocarcinoma (EA), a highly lethal malignancy whose incidence increased more than 600 percent in three decades. BE is a unique in vivo model of human epithelial neoplasia, and the P01 theme of "neoplastic progression in Barrett's esophagus: pathways and prevention" emphasizes the translational research goals of the P01 for 1) cancer risk prediction, 2) modifiable risk and protective factors for cancer prevention and 3) individualized interventions tailored to risk in BE and other neoplasms whose early stages are less amenable to investigation. The study design is a prospective investigation of the Seattle BE Cohort, one of the largest and best characterized in the world. All data will be derived from this cohort, maintained by Core B (Clinical Research). Project 1 (Clonal Evolution) will investigate epigenetic and genomic instability and clonal evolution in BE to evaluate selected LOH, copy number change, CpG island methylation and DNA content abnormalities to determine the extent to which they predict neoplastic progression. Project 1 will develop clinically compatible DNA biomarker platforms for validated markers. Project 2 (Epidemiology) hypothesizes that obesity and reflux combine to increase risk of EA through a network of mechanisms, including metabolic abnormalities associated with the insulin resistance syndrome, inflammation and oxidative stress. It seeks to identify effective prevention strategies and develop a predictive risk model of neoplastic progression in BE that can be used clinically. Project 3 (Genetic Instability) will examine some of the earliest processes contributing to neoplasia in BE and hypothesizes that chronic inflammation and genotoxic stress predispose to telomere shortening and genetic instability at chromosomal fragile sites. The P01 is highly collaborative and all projects and cores interact. Clonal evolutionary markers, epidemiology assessments, and measures of instability provided by Projects 1, 2 and 3, respectively, are shared resources to advance common goals. These interactions are facilitated by Core C (Biostatistics and Evolutionary Analysis), which provides input into all study design as well as a framework for analysis of the complicated datasets of the projects. Core A (Leadership) provides a vehicle for inter project and core communications.

描述（由申请人提供）：此P01更新申请来自经验丰富的研究团队，该团队将调查Barrett的食管（BE），Barrett的食管唯一既定的食管腺癌（EA）的先驱，这是一种高度致命的恶性肿瘤，其发病率在三个中增加了600％以上几十年。 BE是人类上皮肿瘤的体内模型独特，并且是“巴雷特食管中的肿瘤进展：途径和预防”的P01主题，强调了P01的转化研究目标，以实现1）癌症风险预测，2）修改性风险和保护性因素为了预防癌症和3）针对BE风险和其他肿瘤量身定制的个性化干预措施，其早期阶段不太适合研究。研究设计是对西雅图的前瞻性调查，这是世界上最大，最佳特征的研究之一。所有数据将源自该队列，由Core B（临床研究）维持。项目1（克隆进化）将研究表观遗传和基因组不稳定性和克隆进化，以评估选定的LOH，拷贝数变化，CpG岛甲基化和DNA含量异常，以确定它们预测肿瘤进展的程度。项目1将开发临床上兼容的DNA生物标志物平台，用于经过验证的标记。项目2（流行病学）假设肥胖和反流结合通过机制网络来增加EA的风险，包括与胰岛素抵抗综合征，炎症和氧化应激相关的代谢异常。它试图确定有效的预防策略，并开发可在临床上使用的肿瘤发展的预测风险模型。项目3（遗传不稳定性）将检查在BE中导致肿瘤的一些最早的过程，并假设慢性炎症和遗传毒性应激倾向于在染色体脆弱部位缩短端粒缩短和遗传不稳定性。 P01是高度协作的，所有项目和核心都相互作用。克隆进化标记，流行病学评估和项目1、2和3分别提供的不稳定性措施是共同的资源以促进共同目标。这些相互作用由Core C（生物统计学和进化分析）促进，该核心提供了所有研究设计的意见以及分析项目复杂数据集的框架。核心A（领导力）为间项目和核心通信提供了一种工具。