Barrett's Esophagus

巴雷特食管

基本信息

批准号：
10919013
负责人：
Christian Abnet
金额：
$ 2.46万
依托单位：
DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
依托单位国家：
美国
项目类别：
财政年份：
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/10919013
关键词：
Adenocarcinoma Algorithms Androgens Barrett Epithelium Barrett Esophagus Case/Control Studies Cells Chemicals Clinical Cohort Studies Costs and Benefits Data Databases Diagnosis Disease Endoscopy Epithelial Cells Epithelium Equation Esophageal Adenocarcinoma Esophagitis Esophagus Estrogens Etiology Exposure to Gastroenterology Gastroesophageal reflux disease General Population General Practices Goals Hepatology Hormones Incidence Individual Journals Laboratories Lesion Link Malignant Neoplasms Malignant neoplasm of esophagus Manuscripts Medical History Medicare Metabolic syndrome Metaplasia Modality Natural History Patients Population Prognostic Marker Publications Publishing Reflux Research Research Personnel Resources Risk Risk Factors Squamous Cell Staging Survival Rate Testing Tissues Triage United States bile salts billing data cancer epidemiology cancer risk clinical practice cohort comparative data harmonization diagnostic biomarker diagnostic value disease natural history disorder control follow-up genotoxicity high risk indexing inflammatory marker mortality risk prognostic

项目摘要

This project covers a broad range of studies which focus on elucidating risk factors for, and the natural history of, esophageal adenocarcinoma (esophageal cancer) and the precursor lesion Barretts esophagus (aka Barrett esophagus). Barretts esophagus is a metaplastic change in the lower esophagus which is characterized by the replacement of the native squamous cell epithelium with a glandular-type of epithelium. This metaplastic change is thought to be primarily the result of genotoxic damage induced by gastroesophageal refluxacid and bile salts reflux up into the esophagus, exposing cells not equipped to deal with these reactive chemicals. Re-epithelization with the metaplastic Barretts epithelium provides for a tissue which is better able to withstand the exposure to such compounds. However, it also increases the risk of esophageal adenocarcinoma approximately 10-50 fold that of the general population. The incidence of esophageal adenocarcinoma has increased over 650% in the United States over the last 35 years and most individuals present with late stage malignancies, resulting in a 5-year survival rate of less than 20%. This indicates that researchers need to be able to better identify those at high risk and Barretts esophagus is a good starting point. However, although this metaplasia greatly increases the risk of esophageal adenocarcinoma relative to the general population, the absolute risk remains low at around 0.5% or 1 in 200 patient years of follow-up. This is because approximately 90% of individuals who develop esophageal adenocarcinoma are diagnosed at their first (index) endoscopy. Thus, not only do we need to be able to better identify those with high risk (Barretts esophagus) in the general population, we also need to be able to triage these individuals into high and low risk groups so that surveillance resources can be focused on those who most need them, which would make the cost-benefit equation of surveillance endoscopy more attractive. Therefore, the ultimate goals of all the studies within this project seek to better understand the natural history of this disease, risk factors for progression, diagnostic markers and modalities with high sensitivity, and prognostic biomarkers for efficient triaging of risk.The Barrett's Esophagus Consortium project (CAS ID:10593) is a pooling project that brings together and harmonizes data from eight case-control studies of Barrett's esophagus and fourteen case-control studies of esophageal adenocarcinoma. The consortium has published many articles, details of which can be seen at http://beacon.tlvnet.net/ The Esophageal Cancer in SEER-Medicare project (CAS ID:10633) is assessing metabolic syndrome in relation to Barrett's esophagus (published in Journal of Clinical Gastroenterology) and esophageal adenocarcinoma (manuscript submitted) as well as the comparative utility of staging modalities in relation to survival following diagnosis of esophageal adenocarcinoma (published in Cancer). We are also assessing whether there is are demographic, medical history, and survival differences in esophageal adenocarcinoma by whether there was a prior diagnosis of the precursor condition Barrett's esophagus (submitted for publication). A new project will assess whether we can develop an algorithm to accurately identify diagnoses of esophageal adenocarcinoma using Medicare billing data alone.The CPRD EAC Progression Study has assessed whether metabolic syndrome is a risk factor for progression from Barretts esophagus to esophageal adenocarcinoma. This analysis is based in the Clinical Practice Research Datalink (CPRD) which was formerly called the General Practice Research Database (GPRD). The manuscript has been published in Cancer Epidemiology. In the Hormones in Barrett's Esophagus project (CAS ID:10638) we have assessed circulating androgens and estrogens in Barrett's esophagus patients compared with gastroeosphageal reflux disease controls in the BEEDS study based at the Walter Reed (published in Clinical Gastroenterology and Hepatology). We are currently assessing similar exposures in a second Barrett's esophagus population for external replication (manuscript being drafted) as well as expansion to esophageal cancer (adenocarcinoma) using three cohort studies.The Kaiser BE Cohort project has enabled us to assess cancer and mortality risks amongst a large Barretts esophagus cohort. These analyses will provide evidence that is directly applicable for a Barretts esophagus population undergoing surveillance. The manuscript has been submitted for publication.The inflammation markers and esophageal adenocarcinoma (CAS 10731) is beinging together esophageal adenocarcinoma cases and controls from seven cohorts. We are assessing a suite of circulating inflammation markers and testing whether these are associated with risk of developing esophageal adenocarcinoma. Laboratory analyses are currently being conducted. All of these projects are closely aligned to the aims of elucidating the etiology of Barrett's esophagus and esophageal adenocarcinoma as well as providing potential utility for diagnostics and prognostics.

该项目涵盖了广泛的研究，重点是阐明食道腺癌（食管癌）和前体病变贝雷特食管（aka barrett食管）的自然史的危险因素和自然史。巴雷特食道是下食道的一种化生变化，其特征是用上皮的腺体型替换天然鳞状细胞上皮。这种化生变化被认为主要是胃食管反流酸引起的遗传毒性损伤的结果，而胆汁盐会反流入食道，暴露于无法处理这些反应性化学物质的细胞。用化生式贝雷特上皮的重新上述为组织提供了能够承受这种化合物的暴露的组织。但是，这也增加了食管腺癌的风险约为一般人群的10-50倍。在过去的35年中，美国食管腺癌的发病率在美国增加了650％以上，大多数人出现了晚期恶性肿瘤，导致5年的存活率低于20％。这表明研究人员需要能够更好地识别高风险的人，而巴雷特食管是一个很好的起点。然而，尽管这种化学大大增加了食管腺癌相对于普通人群的风险，但绝对风险在200名患者随访年中的0.5％或1个左右较低。这是因为在第一次（指数）内窥镜检查中诊断出患食道腺癌的患者中约有90％。因此，我们不仅需要能够更好地识别普通人群中患有高风险的人（Barretts食管），而且我们还需要能够将这些人分为高和低风险群体，以便可以将监视资源重点放在那些最需要它们的人，这将使监视内窥镜检查的成本效益方程更具吸引力。因此，该项目中所有研究的最终目标旨在更好地了解这种疾病的自然历史，进展的危险因素，诊断标记和具有高灵敏度的方式以及预后的生物标志物，以有效地危险。（CAS ID：10593）是一个合并项目，它汇集了八项对巴雷特食管的病例对照研究和食管腺癌的14例病例对照研究的数据。该财团发表了许多文章，可以在http://beacon.tlvnet.net/ Seer-Medicare Project（CAS ID：10633）中查看其详细信息。临床胃肠病学杂志）和食管腺癌（手稿提交）以及分期模态在诊断食管腺癌（发表在癌症中）后的生存相关的比较效用。我们还评估是否有人口统计学，病史和食管腺癌的生存差异，是否有先前诊断为先前的疾病Barrett的食管（已提交出版）。一个新项目将评估我们是否可以仅使用Medicare计费数据来准确识别食管腺癌的诊断。CPRDEAC进展研究评估了代谢综合征是否是从Barretts食管到食管食管腺癌的危险因素。该分析基于临床实践研究数据链接（CPRD），该研究数据库以前称为通用实践研究数据库（GPRD）。该手稿已发表在癌症流行病学上。在Barrett的食道项目（CAS ID：10638）的激素中，我们评估了Barrett食管患者中循环的雄激素和雌激素，与沃尔特·里德（Walter Reed）的胃磷酸反复疾病对照相比，与胃磷酸化反复反应疾病对照相比（发表于临床胃肠病学和易爆术学）。我们目前正在使用三个同类研究中的第二个巴雷特食管种群中评估第二次巴雷特食管种群中的外部复制（手稿）以及对食道癌（腺癌）的扩张。大型巴雷特食道同类。这些分析将提供直接适用于接受监视的食道食管人群的证据。该手稿已提交出版。炎症标记和食管腺癌（CAS 10731）正在一起食管腺癌病例和对照组的七个同类群体。我们正在评估一套循环炎症标记物，并测试它们是否与患食道腺癌的风险有关。目前正在进行实验室分析。所有这些项目都与阐明Barrett食管和食管腺癌的病因的目的紧密一致，并为诊断和预后提供了潜在的实用性。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pathogenesis and progression of oesophageal adenocarcinoma varies by prior diagnosis of Barrett's oesophagus.

DOI：
10.1038/bjc.2016.344
发表时间：
2016-11-22
期刊：
BRITISH JOURNAL OF CANCER
影响因子：
8.8
作者：
Cook, Michael B.;Drahos, Jennifer;Wood, Shannon;Enewold, Lindsey;Parsons, Ruth;Freedman, Neal D.;Taylor, Philip R.;Ricker, Winnie;Abnet, Christian C.
通讯作者：
Abnet, Christian C.

Circulating Sex Hormones Are Associated With Gastric and Colorectal Cancers but Not Esophageal Adenocarcinoma in the UK Biobank.

DOI：
10.14309/ajg.0000000000001045
发表时间：
2021-03-01
期刊：
The American journal of gastroenterology
影响因子：
0
作者：
McMenamin ÚC;Liu P;Kunzmann AT;Cook MB;Coleman HG;Johnston BT;Cantwell MM;Cardwell CR
通讯作者：
Cardwell CR

Metabolic syndrome in relation to Barrett's esophagus and esophageal adenocarcinoma: Results from a large population-based case-control study in the Clinical Practice Research Datalink.