Helicobacter pylori subtypes, inflammation, and gastric cancer risk

描述（由申请人提供）：炎症已被假设参与多种癌症的病因学，并且新出现的证据暗示慢性炎症的重要作用，由于生物制剂和其他原因，表明癌症是一种未愈合的感染情况。Epplein博士是范德比尔特大学（Vanderbilt University）的终身流行病学助理教授，该职业发展奖将为她提供进一步研究感染和炎症与癌症风险相关的职业所需的培训。虽然Epplein博士在博士和博士后期间在流行病学方法学、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来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侧重于幽门螺杆菌、宿主炎症细胞因子和胃癌风险，将作为一个培训机会，使Epplein博士能够扩展她的专业知识，并成为感染、炎症和癌症研究的领导者。在这个培训项目中，范德比尔特大学的分子流行病学专家（Wei Zheng）、胃癌专家（Pelayo Correa）和幽门螺杆菌生物学专家（Richard Peek）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，胃癌是世界上第二大癌症死亡原因。幽门螺杆菌是一种存在于世界上大约一半人口胃中的革兰氏阴性螺旋菌，通常在儿童时期获得，是目前已知的最强的胃癌危险因素。虽然在某些幽门螺杆菌菌株中发现的CagA和VacA蛋白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发现了15种不同的幽门螺杆菌蛋白。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开展一项巢式病例对照研究，以调查胃癌风险与以下因素的关系：1)幽门螺杆菌菌株特异性感染；2)宿主全身性炎症因子；3)幽门螺杆菌感染与宿主炎症因子的潜在相互作用。本研究的最终目的是帮助更适当地评估总体风险，以确定胃癌的一级和二级预防的高危人群。凭借该CDA提供的知识和经验，Epplein博士将准备获得建立胃癌病因学多学科研究项目所需的资金，并将该主题的研究扩展到其他高风险人群，如低收入非洲裔美国人。此外，这将为她建立一个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。

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.