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: 8481198
• 负责人: MEIRA EPPLEIN
• 金额: $ 13.27万
• 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/8481198
• 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）：已经假设炎症与多种癌症的病因有关，而新兴的证据则暗示了由于生物学剂和其他原因，慢性炎症的重要作用，这表明癌症是一种未造成的感染状况。该职业发展奖将为范德比尔特大学（Vanderbilt University）的终身训练助理教授Epplein博士提供，并在与癌症风险有关的情况下进一步培训了她在感染和炎症研究方面所需的培训。尽管Epplein博士在博士学位和博士后经历期间在流行病学方法论，统计分析和科学写作方面都接受了出色的培训，但她需要进一步的培训，以获得她所选择的炎症和癌症研究领域的专业知识。该奖项中提出的特定项目的重点是幽门螺杆菌，宿主炎症细胞因子和胃癌风险，将成为培训机会，以便Epplein博士可以扩大她的专业知识并成为感染，炎症和癌症研究的领导者。对于这个培训项目，与分子流行病学专家（WEI Zheng），胃癌（Pelayo Correa）和范德比尔特大学（Vanderbilt University）的H. Pylori Biology（Richard Peek）相比，她无法得到更好的服务。她的研究计划旨在通过对高危人群中宿主和细菌因素的分析，旨在进一步了解胃癌病因，这是胃癌的第二大死亡原因。 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个不同的幽门螺杆菌蛋白。同时，宿主的炎症性和胃癌风险之间已经看到了牢固的关联，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创造了胃癌生长的肥沃地。为了研究这些复杂的关系，Epplein博士将在上海健康研究中进行一项嵌套的病例对照研究，以研究胃癌风险与以下方面的风险：1）幽门螺杆菌特异性感染； 2）宿主系统性炎症细胞因子； 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，这项研究旨在有助于更适当地评估总体风险，以识别胃癌初级和二级预防的高风险受试者。借助此CDA提供的知识和经验，Epplein博士将准备确保建立胃癌病因的多学科研究计划所必需的资金，从而将她对这一主题的研究扩展到其他高风险人群，例如低收入的非洲非裔美国人。此外，这将为她提供建立独立的长期职业，更广泛地关注感染，炎症和癌症。