Helicobacter pylori subtypes, inflammation, and gastric cancer risk

描述（由申请人提供）：炎症被假设参与多种癌症的病因学，并且新出现的证据表明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感染的情况。Epplein博士是范德比尔特大学流行病学的终身助理教授，她将获得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博士在她的博士和博士后经历中接受了流行病学方法，统计分析和科学写作方面的出色培训，但她需要进一步培训，以获得她所选择的炎症和癌症研究领域的专业知识。该奖项中提出的具体项目，专注于幽门螺杆菌，宿主炎性细胞因子和胃癌风险，将作为培训机会，以便Epplein博士可以扩展她的专业知识，并成为感染，炎症和癌症研究的领导者。在这个培训项目中，她得到了分子流行病学（魏征）、胃癌（佩拉约·科雷亚）和H。范德比尔特大学的幽门生物学（理查德·皮克）。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，胃癌是全球癌症死亡的第二大常见原因。H.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人口的胃中，通常在儿童时期获得，目前是胃癌最强的已知危险因素。幽门螺杆菌一直被认为是致病因子，最近的新研究探索了幽门螺杆菌的多样性。pylori中发现了15种不同的H。pylori蛋白与此同时，宿主炎症特征与胃癌风险之间有很强的相关性，这表明它是H。幽门螺杆菌菌株特异性感染和宿主炎症反应，创造了胃癌生长的肥沃土壤。为了研究这些复杂的关系，Epplein博士将在上海健康研究中进行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）H。pylori菌株特异性感染; 2）宿主全身性炎性细胞因子;和3）H.幽门螺杆菌感染和宿主炎性细胞因子。最终，本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。Epplein博士将准备获得必要的资金，以建立一个关于胃癌病因学的多学科研究计划，将她对这一主题的研究扩展到其他高风险人群，如低收入的非洲裔美国人。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.