Metabolome Risk Factors for Barrett's Esophagus

巴雷特食管的代谢组危险因素

• 批准号: 8118930
• 负责人: JOEL H RUBENSTEIN
• 金额: $ 7.7万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118930
• 关键词: Adult; Anthropometry; Barrett Esophagus; Behavioral; Biological Assay; Blood; Blood Circulation; Blood specimen; Cachexia; Cancerous; Colon Carcinoma; Colonoscopy; Complex; Data; Data Set; Deglutition Disorders; Development; Diagnosis; Diet; Diet Habits; Dietary intake; Disease Association; Distal; Endoscopy; Enrollment; Environmental Risk Factor; Epidemiology; Epigenetic Process; Esophageal; Esophageal Adenocarcinoma; Esophageal mucous membrane; Fasting; Funding; Gastroesophageal reflux disease; Genetic; Goals; Habits; In Vitro; Incidence; Intestinal Metaplasia; Lesion; Life Style; Malignant - descriptor; Malignant Neoplasms; Measurement; Mechanics; Mediator of activation protein; Mentored Patient-Oriented Research Career Development Award; Metabolic; Metabolic Pathway; Methods; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Outcome; Outcomes Research; Pattern; Peptides; Phenotype; Physical activity; Plasma; Precancerous Conditions; Premalignant; Questionnaires; Reflux; Research; Research Methodology; Risk; Risk Factors; Screening procedure; Specimen; Staging; Stratification; Symptoms; Techniques; Tobacco; Tobacco use; Translational Research; United States; Work; adipokines; cohort; cost effective; diagnostic accuracy; high throughput technology; improved; men; metabolomics; mortality; novel strategies; obesity risk; patient oriented; programs; public health relevance; sedentary; small molecule; translational study

DESCRIPTION (provided by applicant): The incidence of esophageal adenocarcinoma is among the most rapidly rising in the United States. The cancer has been associated with obesity, sedentary life style, and Western diet. Barrett's esophagus is an intestinal metaplasia of the distal esophageal mucosa that is an accepted premalignant lesion associated with esophageal adenocarcinoma. Barrett's esophagus is associated with prior symptoms of gastroesophageal reflux disease, and the association of Barrett's esophagus with obesity is likely due at least in part to a mechanical effect promoting reflux. But obesity is associated with other cancers as well, for which no mechanical explanation exists, and alterations in levels of circulating peptide adipokines have been associated with a number of cancers and pre-cancerous conditions, including Barrett's esophagus and esophageal adenocarcinoma. Peptides are just one broad type of molecule found in circulation. Hundreds of small molecule metabolites circulate in blood. The "metabolome" refers to the global pattern of small molecule metabolites. The metabolome is a richly detailed phenotype that reflects an outcome of complex interactions of genetic, epigenetic, behavioral, and environmental factors. High-throughput platforms for the analysis of the metabolome ("metabolomics") have recently been developed. Panels of metabolites ("metabolomic profiles") might represent a particularly efficient method for stratifying risk for the obesity-related outcome of Barrett's esophagus, and may unveil new understandings of mechanisms by which obesity promotes cancer. The proposed study utilizes specimens from an ongoing inception cohort of Barrett's esophagus cases and noncases, funded by the PI's NIDDK K23 award "The Epidemiology of Adipokines in Barrett's Esophagus" (K23DK079291). We propose using high-throughput technology to assay the metabolome in stored plasma, and propose a Bayesian analytic approach to handle the very rich dataset provided by metabolomics. The proposed specific aims are to: 1. Estimate the effect of specific plasma metabolomic profiles on the risk of Barrett's esophagus in adult men. 2. Estimate the mediator effect of the specific metabolomic profiles for conventional predictors of Barrett's esophagus, including obesity, dietary intake, physical activity, and tobacco use. 3. Determine whether the metabolomic profiles improve the diagnostic accuracy over conventional predictors for Barrett's esophagus. The proposed translational study will apply the promising technique of metabolomics to patient-centered research, likely resulting in identification of metabolic pathways involved in obesity's promotion of malignancy, and possibly novel strategies of risk-stratification for esophageal adenocarcinoma. The study would continue work along the PI's long-term research goal to use outcomes and translational research methods to develop cost-effective strategies for reducing mortality from esophageal adenocarcinoma. PUBLIC HEALTH RELEVANCE: The incidence of esophageal adenocarcinoma is among the most rapidly rising in the United States. This study aims to identify and estimate the effect of specific metabolic profiles circulating in the blood on the risk of developing Barrett's esophagus, a premalignant lesion associated with esophageal adenocarcinoma. If so, measurement of these metabolites may be useful in a screening program.

描述（由申请人提供）：食管腺癌的发生率是美国最快的增长之一。癌症与肥胖，久坐的生活方式和西方饮食有关。巴雷特的食管是远端食管粘膜的肠道化生，是与食管腺癌相关的公认的预抗病变。巴雷特的食管与胃食管反流疾病的先前症状有关，而巴雷特的食管与肥胖症的关联至少可能部分是由于促进反流的机械作用。但是肥胖症也与其他癌症有关，为此，不存在机械解释，循环肽脂肪因子水平的改变与许多癌症和癌前病情有关，包括Barrett的食管和食管食管腺癌。肽只是循环中发现的一种广泛的分子。数百个小分子代谢物在血液中循环。 “代谢组”是指小分子代谢物的全球模式。代谢组是一种详细的表型，反映了遗传，表观遗传学，行为和环境因素的复杂相互作用的结果。最近已经开发了用于分析代谢组（“代谢组学”）的高通量平台。代谢产物（“代谢组谱”）的面板可能代表了一种特别有效的方法，可以使Barrett食管与肥胖相关结果的风险进行分层，并可能揭示对肥胖促进癌症的机制的新理解。拟议的研究利用了由Barrett的食管病例和非案例的持续构成的标本，由PI的NIDDK K23奖资助“ Barrett食管中脂肪因子的流行病学”（K23DK079291）。我们建议使用高通量技术分析存储的血浆中的代谢组，并提出了一种贝叶斯分析方法来处理代谢组学提供的非常丰富的数据集。拟议的具体目的是： 1。估计特定血浆代谢组学对成年男性食管的风险的影响。 2。估计特异性代谢组谱对巴雷特食管的常规预测指标的介体效应，包括肥胖，饮食摄入，体育活动和烟草使用。 3.确定代谢组谱是否提高了巴雷特食管的常规预测因子的诊断准确性。 拟议的翻译研究将对以患者为中心的研究应用有前途的代谢学技术，可能导致鉴定肥胖促进恶性肿瘤涉及的代谢途径，以及可能是食管腺癌的风险分层的新型策略。该研究将继续遵循PI的长期研究目标，以使用结果和翻译研究方法来制定降低食管腺癌死亡率的具有成本效益的策略。 公共卫生相关性：食管腺癌的发病率是美国最快的增长之一。这项研究旨在识别和估计血液中循环的特定代谢特征对发展巴雷特食管的风险，巴雷特食管的风险是与食管腺癌相关的前病变。如果是这样，这些代谢物的测量可能在筛查程序中很有用。