Helicobacter pylori subtypes, inflammation, and gastric cancer risk

描述(申请人提供)：炎症被认为与多种癌症的病因有关，新出现的证据表明，由于生物因素和其他原因，慢性炎症起着重要作用，表明癌症是一种未愈合的感染情况。这项职业发展奖将为范德比尔特大学终身教授流行病学助理教授Epplein博士提供所需的培训，以促进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博士在她的博士和博士后经历中接受了流行病学方法论、统计分析和科学写作方面的出色培训，但她需要进一步的培训才能获得她选择的炎症和癌症研究领域的专业知识。该奖项中建议的具体项目，重点是幽门螺杆菌、宿主炎症细胞因子和胃癌风险，将作为一个培训机会，使Epplein博士能够扩大她的专业知识，成为感染、炎症和癌症研究的领先者。在这个培训项目中，范德比尔特大学的分子流行病学(魏征)、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，胃癌是全球第二大最常见的癌症死亡原因。幽门螺杆菌是一种革兰氏阴性螺旋菌，存在于世界上大约一半的人口的胃中，通常是在儿童时期获得的，目前是已知的胃癌最大的危险因素1-4，虽然在一些幽门螺杆菌菌株中发现的蛋白CagA和VacA一直被确定为毒力因子，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。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，这表明正是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嵌套病例对照研究，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)宿主全身炎症细胞因子；以及3)幽门螺杆菌感染和宿主炎症细胞因子之间的潜在相互作用。最终，这项研究的目的是帮助更恰当地评估总体风险，以确定胃癌一级和二级预防的高危对象。有了CDA提供的知识和经验，Epplein博士将准备获得必要的资金，以建立一个关于胃癌病因的多学科研究计划，将她对这一主题的研究扩大到其他高危人群，如低收入的非裔美国人。此外，这将为她建立一个独立的长期职业生涯奠定基础，更广泛地专注于感染、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.