Gene-environment EBV Interactions in the Etiology of Nasopharyngeal Carcinoma (NP

描述：鼻咽癌病因中的基因-环境EBV相互作用摘要/摘要我们的长期目标是为识别未分化鼻咽癌(NPC)的高危个体和制定有效的一级和二级预防措施提供科学依据。在中国(鼻咽癌在一些地区是地方性的)，一些较小的、通常以医院为基础的研究表明，遗传易感性、EB病毒感染和其他环境因素在鼻咽癌的病因中都是重要的。然而，之前没有一项研究允许同时量化它们的作用，以及对它们之间相互作用的详细分析。因此，我们的具体目标是1)确定a)特定EBV毒株的主要影响，b)饮食因素，c)吸烟和d)参与致癌物质代谢、DNA修复、细胞受体和细胞因子的产生和调节的基因以及染色体4和5上的候选基因的变异；2)确定关键的基因-环境-EBV相互作用。基于波士顿哈佛公共卫生学院、中国的两个主要癌症中心、斯德哥尔摩的卡罗林斯卡研究所、弗里蒙特的北加州癌症中心和西雅图的弗雷德·哈钦森癌症中心的集体经验，以及广泛的规划和试点研究，我们建议在中国南部两个世界上鼻咽癌发病率最高的省份进行一项以人群为基础的病例对照研究。在总计2000例经组织病理证实的鼻咽癌病例和同等数量的人口对照中，我们将进行面对面访谈，采集肿瘤组织和血液，并进行基因分型和其他实验室分析。有了拟议的大型研究，我们将有足够的统计能力来检测遗传和环境暴露的主要影响，这些影响的相对风险低至1.2，以及中等规模的相互作用。重要的是，我们还将开发一个组织、血清和DNA的生物库，供其他研究人员和未来的遗传学研究使用。我们认为这项研究是及时的，因为中国机构的复杂性直到最近才增加到在城市和农村地区进行大规模基于人群的分子流行病学研究已经成为可能。此外，最近高通量技术的改进使进行大规模研究检查基因-环境-病毒相互作用成为可能。鼻咽癌(NPC)是东南亚最常见的癌症之一，但人们对其病因知之甚少。这项研究将在中国南部调查鼻咽癌的遗传、病毒和环境风险因素，那里的鼻咽癌发病率是世界上最高的之一。我们的目标是找到预防鼻咽癌的新方法，以及改进对高危个体的识别，以便早期发现和成功治疗鼻咽癌。

DESCRIPTION: Gene-Environment EBV Interactions in the Etiology of NPC Summary/Abstract Our long-term objective is to provide a scientific basis for identifying individuals at high risk for undifferentiated nasopharyngeal carcinoma (NPC) and for instituting effective primary and secondary prevention measures. In China (where NPC is endemic in some areas) several smaller, often hospital- based studies have indicated that genetic susceptibility, Epstein-Barr virus (EBV) infection and other environmental factors are all important in the etiology of NPC. However, no previous study has allowed the simultaneous quantification of their roles, along with detailed analyses of the interplay among them. Therefore, our specific aims are 1) to identify the main effects of a) specific EBV strains, b) dietary factors, c) smoking and d) variation in genes Involved in carcinogen metabolism, DNA repair, production and regulation of cellular receptors and cytokines as well as candidate genes on chromosome 4 and 5; and 2) to identify key gene-environment-EBV interactions. Building on the collective experience of the Harvard School of Public Health in Boston, two major cancer centers in China, Karolinska Institute in Stockholm, the Northern California Cancer Center in Fremont, and the Fred Hutchinson Cancer Center in Seattle, and on extensive planning and pilot studies, we propose a population-based case-control study in two provinces in southern China with the world's highest incidence of NPC. With a total of 2,000 incident cases with histopathologically confirmed NPC and an equal number of population controls, we will carry out face-to-face interviews, collect tumor tissue and blood, and perform genotyping and other laboratory analyses. With the proposed large size of the study, we will have sufficient statistical power to detect main effects of genetic and environmental exposures conferring a relative risk as low as 1.2, along with moderate-sized interactions. Importantly, we will also develop a biologic bank of tissue, serum and DNA, which will be made available for other investigators and for future genetic studies. We consider this study timely because the sophistication of the Chinese institutions only recently has increased to the point where large-scale population-based molecular epidemiologic studies in both urban and rural areas have become feasible. In addition, recent improvements in high-throughput technology now make it feasible to conduct a large-scale study examining gene-environment-virus interactions. NPC Narrative: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southeast Asia, yet little is known about its causes. This study will examine genetic, viral, and environmental risk factors for NPC in southern China, where NPC rates are among the highest in the world. Our goal is to identify new ways to prevent NPC, as well as to improve the identification of high-risk individuals for early detection and successful treatment of NPC.