Barriers to Early Detection of Esophageal Adenocarcinoma

食管腺癌早期发现的障碍

• 批准号: 8110845
• 负责人: Katie S Nason
• 金额: $ 16.36万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110845
• 关键词: Address; Antacids; Award; Awareness; Barrett Esophagus; Biological Markers; Biology; Calculi; Cancer Control; Cancer Patient; Carcinogen Screening; Carcinogenesis Mechanism; Caring; Clinical; Clinical Sciences; Clinical Trials; Cross-Sectional Studies; Data; Detection; Development; Diagnosis; Discipline; Disease; Disease Progression; Distal; Dysplasia; Early Diagnosis; Elements; Endoscopy; Epidemiology; Epigenetic Process; Esophageal; Esophageal Adenocarcinoma; Esophageal Neoplasms; Esophagogastric Junction; Exposure to; Foundations; Funding; Future; Gastroesophageal reflux disease; Goals; Health; Health Benefit; Health Insurance; Health Resources; Healthcare; Healthcare Systems; Incidence; Intervention; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Lesion; Location; Malignant Neoplasms; Malignant neoplasm of esophagus; Measurement; Medical; Mentors; Mentorship; Metaplasia; Mission; Modeling; Mutation; National Cancer Institute; Newly Diagnosed; Obesity; Pathologic; Pathway interactions; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Physicians; Positioning Attribute; Prevalence; Prevention; Primary Health Care; Prospective Studies; Proteome; Proteomics; Provider; Public Health; Recording of previous events; Reflux; Research; Research Design; Research Personnel; Research Support; Research Training; Risk; Risk Factors; Role; Sampling; Screening procedure; Self Medication; Serum; Smoking; Specimen; Staging; Stratification; Symptoms; System; Time; Tissues; Training; Training and Education; Translating; Transportation; Tumor Biology; Universities; Work; advanced disease; base; cancer prevention; carcinogenesis; career; career development; improved; instrument; meetings; mortality; novel; prevent; socioeconomics; success; tool; tumor

DESCRIPTION (provided by applicant): Esophageal adenocarcinoma (EAC) incidence is increasing rapidly and endoscopy-based screening has not reduced mortality despite targeting patients with known risk factors [GERD, obesity, smoking and Barrett's esophagus (BE)]. This proposal describes a five-year training and research plan to develop expertise in the control and prevention of EAC through a K07 career-development award. The long-term research goal is to develop clinical prediction models that enable timely utilization of health resources in the detection of curable EAC. These models would incorporate serum and tissue biomarkers, known risk factors and modifiable patient-medical system interactions, such as barriers to patients presenting for and receiving health care, which might facilitate detection of curable EAC. This proposal has important public health implications in that it seeks to improve risk stratification for patients with EAC by examining deficits in understanding of the patient-medical system interaction while determining differences in underlying biology between EAC with associated BE compared to those without associated BE. The University of Pittsburgh is the ideal venue for this work, offering unparalleled research support, high patient volumes and world-renowned mentorship in EAC biomarkers, epidemiology, screening (Luketich, Vaughan and Jobe), and measurement development (Switzer). The long-term career goal to develop clinical prediction models for EAC will be initiated with the short-term, integrated research and training plan described in this K07 proposal. A novel self-report instrument for use in a cross-sectional study of EAC will be developed to examine the hypothesis that patients presenting with advanced versus early-stage EAC will have a different prevalence and pattern of risk factors (Aim 1) and less effective interactions with the medical system (Aim 2; e.g. lack of regular primary care provider, self- versus physician-directed treatment of GERD). Using the current symptom-based screening paradigm, however, EAC may not be detectable at a curable stage in a large subset of patients if the cancer does not arise from endoscopically visible BE. To address this question, proteomic expression patterns will be determined (Aim 3) between EAC with associated Barrett's esophagus compared to those without associated Barrett's with respect to location (esophageal body versus gastroesophageal junction) and stage. Coursework is proposed that builds upon prior training. Specific expertise in cancer biomarkers, measurement development, and prospective study design, implementation and analysis will be obtained. With strong institutional support and mentoring, the candidate is perfectly positioned to complete the proposed training and research. The findings will provide preliminary data for a R01 to be submitted in the fourth year of the award period. This application has specific relevance to the primary mission of the National Cancer Institute, which is to support education and training in fundamental sciences and clinical disciplines, establishing the groundwork for this candidate's future success as an independently funded researcher in the prevention and control of esophageal cancer.

描述（由申请人提供）：食管腺癌（EAC）发病率正在迅速增加，尽管基于内镜检查的筛查针对的是具有已知危险因素[GERD、肥胖、吸烟和巴雷特食管（BE）]的患者，但并未降低死亡率。该提案描述了一项为期五年的培训和研究计划，旨在通过 K07 职业发展奖培养 EAC 控制和预防方面的专业知识。长期研究目标是开发临床预测模型，以便及时利用卫生资源来检测可治愈的 EAC。这些模型将纳入血清和组织生物标志物、已知的风险因素和可修改的患者-医疗系统相互作用，例如患者就诊和接受医疗保健的障碍，这可能有助于检测可治愈的 EAC。该提案具有重要的公共卫生意义，因为它旨在通过检查对患者与医疗系统相互作用的理解缺陷来改善 EAC 患者的风险分层，同时确定具有相关 BE 的 EAC 与不具有相关 BE 的 EAC 之间的基础生物学差异。匹兹堡大学是这项工作的理想场所，在 EAC 生物标志物、流行病学、筛查（Luketich、Vaughan 和 Jobe）和测量开发（Switzer）方面提供无与伦比的研究支持、大量患者和世界知名的指导。开发 EAC 临床预测模型的长期职业目标将通过本 K07 提案中描述的短期综合研究和培训计划启动。将开发一种用于 EAC 横断面研究的新型自我报告工具，以检验以下假设：晚期 EAC 患者与早期 EAC 患者的危险因素患病率和模式不同（目标 1），并且效果较差与医疗系统的互动（目标 2；例如缺乏正规的初级保健提供者、GERD 的自我治疗与医生指导治疗）。然而，使用当前基于症状的筛查范例，如果癌症不是由内窥镜可见的 BE 引起，那么在很大一部分患者的可治愈阶段，EAC 可能无法检测到。为了解决这个问题，将确定具有相关 Barrett 食管的 EAC 与不具有相关 Barrett 食管的 EAC 在位置（食管体与胃食管交界处）和阶段方面的蛋白质组表达模式（目标 3）。建议以先前培训为基础的课程作业。将获得癌症生物标志物、测量开发以及前瞻性研究设计、实施和分析方面的具体专业知识。凭借强大的机构支持和指导，候选人完全有能力完成拟议的培训和研究。研究结果将为在奖励期第四年提交的 R01 提供初步数据。该申请与国家癌症研究所的主要使命有特定的相关性，即支持基础科学和临床学科的教育和培训，为该候选人未来作为一名独立资助的食管癌预防和控制研究人员的成功奠定基础。