Barrett's Esophagus: Predictors of Progression

巴雷特食管：进展的预测因素

• 批准号: 7483771
• 负责人: BRIAN J REID
• 金额: $ 237.41万
• 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/7483771
• 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）：这份 P01 续签申请来自经验丰富的研究团队，该团队将调查巴雷特食管 (BE)，巴雷特食管是食管腺癌 (EA) 唯一确定的前兆，食管腺癌是一种高度致命的恶性肿瘤，其发病率在三年内增加了 600% 以上。几十年。 BE是一种独特的人类上皮肿瘤体内模型，P01的主题“巴雷特食管的肿瘤进展：途径和预防”强调了P01的转化研究目标：1）癌症风险预测，2）可改变的风险和保护因素癌症预防；3）针对BE和其他肿瘤风险的个体化干预措施，这些肿瘤的早期阶段不太适合调查。该研究设计是对西雅图 BE 队列的前瞻性调查，该队列是世界上规模最大、特征最鲜明的队列之一。所有数据均来自该队列，由 Core B（临床研究）维护。项目 1（克隆进化）将研究 BE 中的表观遗传和基因组不稳定性以及克隆进化，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 将为经过验证的标记物开发临床兼容的 DNA 生物标记物平台。项目 2（流行病学）假设肥胖和反流通过一系列机制（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）结合起来增加 EA 的风险。它旨在确定有效的预防策略并开发可用于临床的 BE 肿瘤进展的预测风险模型。项目 3（遗传不稳定性）将检查一些导致 BE 肿瘤形成的最早过程，并假设慢性炎症和遗传毒性应激容易导致染色体脆弱位点的端粒缩短和遗传不稳定性。 P01 具有高度协作性，所有项目和核心都相互作用。项目 1、2 和 3 分别提供的克隆进化标记、流行病学评估和不稳定性测量是促进共同目标的共享资源。这些相互作用由核心 C（生物统计学和进化分析）促进，它为所有研究设计提供输入以及用于分析项目复杂数据集的框架。核心 A（领导力）提供了项目间和核心沟通的工具。