Helicobacter pylori subtypes, inflammation, and gastric cancer risk

幽门螺杆菌亚型、炎症和胃癌风险

• 批准号: 8294523
• 负责人: MEIRA EPPLEIN
• 金额: $ 13.07万
• 依托单位: VANDERBILT UNIVERSITY
• 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/8294523
• 关键词: Address; African American; Age; Area; Asia; Award; Bacteria; Biological Assay; Biology; Blood specimen; Cancer Etiology; Cause of Death; Central America; Cervix Uteri; Childhood; China; Chinese People; Chronic; Chronic Disease; Cohort Studies; Communities; Complement; Complex; Country; Data; Development; Diagnostic tests; Diet; Disease; Eastern Europe; Employee Strikes; Environment; Environmental Risk Factor; Epidemiology; Etiology; Funding; Future; Goals; Health; Helicobacter Infections; Helicobacter pylori; Hepatitis B Virus; Hepatitis C virus; Human Papillomavirus; IL8 gene; Incidence; Infection; Inflammation; Inflammatory; Inflammatory Response; Interdisciplinary Study; Interferons; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Investigation; K-Series Research Career Programs; Knowledge; Life Style; Light; Liver; Low income; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Mentors; Methodology; Minority; Molecular Epidemiology; Nested Case-Control Study; North America; Population; Postdoctoral Fellow; Primary Prevention; Proteins; Recruitment Activity; Research; Research Personnel; Risk; Risk Factors; Role; Secondary Prevention; Secure; Serologic tests; Smoking; South America; Southeastern Asia; Southeastern United States; Stomach; TNF gene; Time; Training; Training Programs; United States; Universities; Virulence Factors; Virulent; Vulnerable Populations; Woman; Women' s Health; Work; Writing; aged; base; cancer risk; career; cohort; cytokine; experience; health disparity; high risk; inflammatory marker; low socioeconomic status; male health; malignant stomach neoplasm; men; mortality; prevent; professor; programs; prospective; public health relevance; training project

DESCRIPTION (provided by applicant): Inflammation has been hypothesized to be involved in the etiology of multiple cancers, and emerging evidence has implicated an important role of chronic inflammation, due to both biologic agents and other causes, suggesting that cancer is a situation of unhealed infection. This Career Development Award will provide Dr. Epplein, a tenure-track Assistant Professor of Epidemiology at Vanderbilt University, with the training needed to further her career in the research of infection and inflammation as they relate to cancer risk. While Dr. Epplein has had excellent training in epidemiological methodology, statistical analysis, and scientific writing during her doctoral and post-doctoral experiences, she requires further training to gain expertise in her chosen research area of inflammation and cancer. The specific project proposed in this award, focusing on Helicobacter pylori, host inflammatory cytokines, and gastric cancer risk, will serve as a training opportunity so that Dr. Epplein can expand her expertise and become a leader in the study of infection, inflammation, and cancer. For this training project, she could not be better served than by the experts in molecular epidemiology (Wei Zheng), gastric cancer (Pelayo Correa), and H. pylori biology (Richard Peek) at Vanderbilt University. Her research plan seeks to further our understanding of the etiology of gastric cancer, the second most common cause of death from cancer worldwide, through analyses of host and bacterial factors in a high-risk population. H. pylori, a gram-negative spiral bacterium that resides in the stomach of approximately half of the world's population and is generally acquired in childhood, is currently the strongest known risk factor for gastric cancer.1-4 And, while the proteins CagA and VacA that are found in some strains of H. pylori have been consistently identified as virulence factors, very recent new research exploring the diversity of H. pylori has revealed 15 distinct H. pylori proteins. At the same time, a strong association has been seen between host inflammatory profile and gastric cancer risk, suggesting that it is the combination of H. pylori strain-specific infection and host inflammatory response that creates the fertile ground for which gastric cancer to grow. To study these complex relationships, Dr. Epplein will conduct a nested case-control study within the Shanghai Health Studies to investigate the association of gastric cancer risk with: 1) H. pylori strain-specific infections; 2) host systemic inflammatory cytokines; and 3) the potential interactions between H. pylori infection and host inflammatory cytokines. Ultimately this research aims to aid in more appropriately assessing overall risk to identify high-risk subjects for primary and secondary prevention of gastric cancer. With the knowledge and experience provided by this CDA, Dr. Epplein will be prepared to secure the funding necessary to establish a multidisciplinary research program on gastric cancer etiology, expanding her research on this subject to other high-risk populations such as low-income African Americans. Furthermore, it will give her the basis to establish an independent long-term career focusing more broadly on infection, inflammation, and cancer.

描述（由申请人提供）：据推测，炎症与多种癌症的病因有关，并且新出现的证据表明，由于生物制剂和其他原因，慢性炎症发挥着重要作用，这表明癌症是一种未治愈的感染情况。该职业发展奖将为范德比尔特大学流行病学终身助理教授 Epplein 博士提供所需的培训，以进一步推动她在与癌症风险相关的感染和炎症研究方面的职业生涯。虽然 Epplein 博士在博士和博士后经历期间在流行病学方法、统计分析和科学写作方面接受了出色的培训，但她需要进一步的培训才能获得她所选择的炎症和癌症研究领域的专业知识。该奖项提出的具体项目重点关注幽门螺杆菌、宿主炎症细胞因子和胃癌风险，该项目将作为培训机会，使 Epplein 博士能够扩展她的专业知识，成为感染、炎症和癌症研究的领导者。对于这个培训项目，范德比尔特大学的分子流行病学（郑伟）、胃癌（Pelayo Correa）和幽门螺杆菌生物学（Richard Peek）专家为她提供了最好的服务。她的研究计划旨在通过分析高危人群中的宿主和细菌因素，进一步了解胃癌的病因学，胃癌是全世界癌症死亡的第二大原因。幽门螺杆菌是一种革兰氏阴性螺旋细菌，存在于世界大约一半人口的胃中，通常在儿童时期感染，是目前已知的最强的胃癌危险因素。1-4 虽然在某些幽门螺杆菌菌株中发现的蛋白质 CagA 和 VacA 一直被认为是毒力因子，但最近探索幽门螺杆菌多样性的新研究表明，幽门螺杆菌是一种革兰氏阴性螺旋细菌。 15 种不同的幽门螺杆菌蛋白。与此同时，宿主炎症特征与胃癌风险之间存在很强的相关性，这表明幽门螺杆菌菌株特异性感染和宿主炎症反应的结合为胃癌的生长创造了肥沃的土壤。为了研究这些复杂的关系，Epplein 博士将在上海健康研究中心进行一项巢式病例对照研究，以调查胃癌风险与以下因素之间的关联：1) 幽门螺杆菌菌株特异性感染； 2）宿主全身炎症细胞因子； 3）幽门螺杆菌感染与宿主炎症细胞因子之间的潜在相互作用。最终，这项研究旨在帮助更适当地评估总体风险，以确定胃癌一级和二级预防的高风险受试者。凭借该 CDA 提供的知识和经验，Epplein 博士将准备好获得必要的资金，以建立胃癌病因学的多学科研究项目，并将她对该主题的研究扩展到其他高风险人群，例如低收入非裔美国人。此外，这将为她建立独立的长期职业生涯奠定基础，更广泛地关注感染、炎症和癌症。