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

摘要/摘要我们的长期目标是为鉴别未分化鼻咽癌（NPC）高危人群和制定有效的一级和二级预防措施提供科学依据。在中国（鼻咽癌在某些地区流行），一些规模较小、通常以医院为基础的研究表明，遗传易感性、eb病毒（EBV）感染和其他环境因素在鼻咽癌的病因学中都很重要。然而，之前没有研究允许同时量化它们的作用，以及详细分析它们之间的相互作用。因此，我们的具体目标是1)确定a)特定EBV菌株的主要影响，b)饮食因素，c)吸烟和d)参与致癌物代谢，DNA修复，细胞受体和细胞因子的产生和调节的基因变异以及4号和5号染色体上的候选基因；2)鉴定关键基因-环境- ebv相互作用。基于波士顿哈佛大学公共卫生学院、中国两大癌症中心——斯德哥尔摩卡罗林斯卡研究所、弗里蒙特北加州癌症中心和西雅图弗雷德哈钦森癌症中心的共同经验，以及广泛的规划和试点研究，我们建议在中国南方两个世界上鼻癌发病率最高的省份开展一项基于人群的病例对照研究。我们将对2000例经组织病理学证实的NPC病例和同等数量的人群进行面对面访谈，收集肿瘤组织和血液，并进行基因分型和其他实验室分析。由于该研究的规模较大，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，其相对风险低至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口的分子流行病学研究成为可能的程度。此外，最近高通量技术的改进使得进行基因-环境-病毒相互作用的大规模研究成为可能。鼻咽癌（NPC）是东南亚最常见的癌症之一，但对其病因知之甚少。本研究将研究中国南方鼻咽癌的遗传、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。我们的目标是找到预防鼻咽癌的新方法，并提高对高危人群的识别，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.