EPIDEMIOLOGY OF PROGRESSION IN BARRETT'S ESOPHAGUS

巴雷特食管进展的流行病学

• 批准号: 7305720
• 负责人: THOMAS L VAUGHAN
• 金额: $ 26.16万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7305720
• 关键词: Affect; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Apoptosis; Barrett Esophagus; Body Weight Changes; Body fat; Body measure procedure; Cancer Etiology; Cell Proliferation; Characteristics; Chronic; Class; Clinic; Clinical; DEXA; DNA Damage; Data; Deposition; Diet; Disease; Effectiveness; Epidemiology; Epithelium; Equilibrium; Esophageal; Esophageal Adenocarcinoma; Fatty acid glycerol esters; Female; Gastroesophageal reflux disease; Genes; Genetic Polymorphism; Gonadal Steroid Hormones; Immune response; Incidence; Inflammation; Inflammatory; Inhibition of Apoptosis; Insulin Resistance; Insulin Resistance Pathway; Interview; Isoprostanes; Joints; Learning; Length; Leukocytes; Malignant Neoplasms; Measurement; Measures; Mediating; Medical Surveillance; Metabolic; Metabolic Pathway; Methods; Modeling; Neoplastic Processes; Non-Steroidal Anti-Inflammatory Agents; Numbers; Obesity; Outcome; Overweight; Oxidative Stress; Pathway interactions; Patients; Pattern; Persons; Pharmaceutical Preparations; Physical activity; Precancerous Conditions; Predisposition; Prevention; Prevention strategy; Process; Prospective Studies; Proton Pump Inhibitors; Reflux; Research; Risk; Risk Factors; Role; Scanning; Serum; Severities; Stimulation of Cell Proliferation; Symptoms; Syndrome; Telomere Shortening; Translations; Visceral; Weight; Work; abdominal pressure; cigarette smoking; cofactor; cohort; cytokine; follow-up; male; modifiable risk; telomere; tool; treatment trial; tumor progression; waist circumference

The incidence of esophageal adenocarcinoma (EA), a rapidly fatal disease, is increasing more rapidly than any other cancer. Much has been learned recently concerning the causes of EA and its main precancerous condition, Barrett's esophagus (BE). In particular, both gastroesophageal reflux disease (GERD) and obesity have been found to be key modifiable risk factors. However, while GERD appears to be crucial to the neoplastic process, only about 10- 15%of persons with long-standing reflux actually develop BE in their lifetimes, and most do not progress to EA. Similarly, the pathways by which obesity increases risk of EA are not known. Understanding the underlying mechanisms by which they affect risk of BE and progression to EA is crucial to identifying effective prevention strategies. Our overarching model is that obesity and GERD act through a network of inter-relating pathways: metabolic abnormalities associated with the insulin resistance syndrome, inflammation and oxidative stress, and alterations in sex steroid hormone levels; and that these processes jointly act to increase mitogenesis, telomere shortening and DNA damage, and inhibit apoptosis. We hypothesize that the effects of obesity and GERD are modified by a number of factors, including diet, physical activity, visceral fat, use of anti-inflammatory medications, and cigarette smoking, and that polymorphisms in inflammatory pathway and related genes are important determinants of susceptibility. We further hypothesize that systemic measures of short- and long-term inflammation and oxidative stress (e.g., serum cytokine and isoprostane levels, leukocyte telomere length) are significant contributors to a personal predictive risk model of neoplastic progression in BE, which we will develop for translation into the clinic. In the renewal period, we propose to evaluate the independent and joint effects of the above factors on risk of neoplastic progression of BE to EA, and risk of developing selected intermediate outcomes as identified by Projects 1 and 3. This will be accomplished through continued follow up and analyses of a well-characterized cohort of over 500 persons with BE followed for up to 17 years. In summary, our project seeks to identify new treatment targets and methods of prevention, along with tools for stratifying patients according to their clinical risk, a vital aid for surveillance, as well as prevention and treatment trials.

食管腺癌(EA)是一种迅速致命的疾病，其发病率的增长速度比 任何其他癌症。最近关于EA及其主要癌前病变的原因已经了解了很多 病情，巴雷特食道(BE)。特别是，胃食道反流病(GERD)和肥胖 已被发现是关键的可改变的风险因素。然而，尽管GERD似乎对 在肿瘤过程中，只有大约10%-15%的长期反流者实际发生在他们的 一生，而且大多数人不会进步到EA。同样，肥胖增加EA风险的途径是 不知道。了解它们影响BE风险和进展为EA的潜在机制 对于确定有效的预防战略至关重要。我们最主要的模型是肥胖和GERD 通过相互关联的通路网络：与胰岛素抵抗相关的代谢异常 综合症、炎症和氧化应激以及性类固醇激素水平的变化； 这些过程共同作用于增加有丝分裂、端粒缩短和DNA损伤，并抑制细胞凋亡。 我们假设肥胖和GERD的影响被许多因素改变，包括饮食， 体力活动、内脏脂肪、消炎药的使用和吸烟，以及 炎症途径及相关基因的多态性是易感性的重要决定因素。我们 进一步假设短期和长期炎症和氧化应激的系统性措施(例如， 血清细胞因子和异前列腺素水平、白细胞端粒长度)是个人 BE中肿瘤进展的预测风险模型，我们将开发该模型以应用于临床。在……里面 在续期期间，我们建议评估上述因素对风险的独立和联合影响。 BE到EA的肿瘤进展和发生选定的中间结果的风险 项目1和项目3。这将通过持续的后续行动和对具有良好特点的 超过500人的队列，并被跟踪长达17年。总而言之，我们的项目试图确定 新的治疗目标和预防方法，以及根据患者的情况对患者进行分层的工具 临床风险是监测以及预防和治疗试验的重要辅助手段。