Gastric Cancer Epidemiology Initiative in Central America

简介（由申请人提供）：候选人：Douglas Morgan， MD MPH，北卡罗来纳大学医学和胃肠病学助理教授。职业发展计划：候选人将进行指导研究并参加课程，以发展翻译研究和实施的重要技能，发展学术领导能力。该候选人将被定位为美国和拉丁美洲胃癌流行病学的领导者。近期目标：获得以胃癌为重点的癌症、营养学和遗传流行病学方法方面的专业知识。长期目标：通过在中美洲一个高发地区开展深入的流行病学倡议，降低拉丁美洲和美国拉丁裔人口的胃癌死亡率。具体目的：1)确定研究人群的胃癌遗传易感性。2)确定幽门螺杆菌cagA毒力片段是否是一个独立的危险因素。3)评价该地区与胃癌相关的饮食因素。研究方法：在洪都拉斯西部进行基于病例对照的人群研究，这是一个高发病率地区（每年每100万名患者中分别有39名和21名，男性和女性）。我们的初步数据表明，该地区是一个独特的流行病学生态位，具有独特的胃癌遗传和环境易感性。在目的1中，我们将确定宿主风险促炎细胞因子谱（IL-1B, IL-10, TNFa, IL-8）。在目标2中，我们将描述幽门螺杆菌和cagA毒力流行率及其与胃癌的关系。在目标3中，我们将评估饮食风险因素。我们将构建多变量模型来评估遗传、幽门螺杆菌和饮食因素之间的相互作用，据我们所知，这是第一次这样的调查。累计目标登记人数为500例和500例对照。环境：事故病例是在洪都拉斯西部唯一一家地区医院招募的，过去4年来，该医院建立了成功的合作关系。以人口为基础的控制是从该地区的村庄招募的。数据减少和分析，标本处理和标本库在UNC胃肠生物学和疾病中心。指导：主要指导将提供Robert Sandier， MD MPH，胃肠道癌症流行病学的全国领导者。二级指导是由三位成功的研究人员促进的：细菌和幽门螺杆菌毒力的国际领导者（范德比尔特大学Richard Peek博士），营养癌症流行病学家（UNC公共卫生学院Jessie Satia博士）和遗传流行病学家（UNC公共卫生学院Kari North博士）。相关性：胃癌是全球癌症死亡的第二大原因，在拉丁美洲很重要，可以通过筛查、细菌根除和/或饮食干预来预防。本研究通过系统流行病学，将提供详细的病因学信息，以针对拉丁美洲和可能增长的美国拉丁裔人口的干预计划。

DESCRIPTION (provided by applicant): Candidate: Douglas Morgan, MD MPH is an assistant professor of Medicine and Gastroenterology at the University of North Carolina. Career Development Plan: the candidate will conduct mentored research and participate in coursework to develop vital skills in translational research and implementation, to develop academic leadership. The candidate will be positioned to become leader in gastric cancer epidemiology in the U.S. and Latin America. Immediate Objective: to acquire expertise in cancer, nutrition, and genetic epidemiology methods with a focus upon gastric cancer. Long-term Objective: to decrease gastric cancer mortality in Latin America and the U.S. Latino population, through an in-depth epidemiology initiative in a high incidence region in Central America. Specific Aims: 1) Delineate the gastric cancer genetic susceptibility of the study population. 2) Determine if the H. pylori cagA virulence moiety is an independent risk factor. 3) Appraise dietary factors associated with gastric cancer in the region. Research Methods: case-control population-based study in Western Honduras, a region of high incidence (39 and 21 per 100K/year, M and F, respectively). Our preliminary data suggests that the region is a distinct epidemiologic niche, with unique gastric cancer genetic and environmental susceptibility. In aim 1, we will determine the host risk proinflammatory cytokine profile (IL-1B, IL-10, TNFa, IL-8). In aim 2, we will delineate the H. pylori and cagA virulence prevalence, and association with gastric cancer. In aim 3, we will assess dietary risk factors. We will construct multivariate models to assess the interaction between genetic, H. pylori and dietary factors, to our knowledge the first such investigation. Cumulative target enrollment is 500 cases and 500 controls. Environment: incident cases are recruited at the sole district hospital in Western Honduras, the site of an established, successful collaboration over the past 4 years. Population-based controls are recruited from villages, in the region. Data reduction and analysis, specimen processing, and specimen banking is within the UNC Center for Gastrointestinal Biology and Disease. Mentorship: primary mentorship will be provided Robert Sandier, MD MPH, a national leader in gastrointestinal cancer epidemiology. Secondary mentorship is facilitated with three successful researchers: an international leader in bacterial and H. pylori virulence (Dr Richard Peek, Vanderbilt University), a nutrition cancer epidemiologist (Dr Jessie Satia, UNC School of Public Health), and a genetic epidemiologist (Dr. Kari North, UNC School of Public Health). Relevance: gastric cancer is the second leading cause of global cancer mortality, important in Latin America, and preventable through initiatives in screening, bacterial eradication, and/or dietary intervention. This study, through systematic epidemiology, will provide detailed etiologic information, to target intervention programs in Latin America and possibly the growing U.S. Latino population.