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

鼻咽癌 (NP) 病因学中的基因-环境 EBV 相互作用

• 批准号: 7464563
• 负责人: HANS-OLOV ADAMI
• 金额: $ 56.11万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7464563
• 关键词: Accounting; Age; Area; Blood; Boston; California; Cancer Center; Candidate Disease Gene; Carcinogen Metabolism; Case-Control Studies; Cells; Childhood; China; Chinese People; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 4; Consumption; Cytokine Receptors; DNA; DNA Repair; Dietary Factors; Early Diagnosis; Enrollment; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Epstein-Barr Virus Infections; Etiology; Exposure to; Family; Family history of; Food; Food and Beverages; Fruit; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genotype; Goals; Herbal Medicine; Histology; Hospitals; Human Herpesvirus 4; Immune response; Incidence; Individual; Infection; Institutes; Institution; Interview; Laboratories; Malignant Neoplasms; Molecular; Nasopharyngeal Undifferentiated Carcinoma; Nasopharynx Carcinoma; Numbers; Pilot Projects; Population; Population Control; Predisposition; Preserved Foods; Production; Prophylactic treatment; Province; Public Health Schools; Rate; Relative Risks; Research; Research Personnel; Risk; Role; Secondary Prevention; Serum; Smoke; Smoking; Southeastern Asia; Susceptibility Gene; Testing; Tissue Banking; Tobacco smoke; Tumor Tissue; Undifferentiated; Variant; Vegetables; Virus; Virus Activation; Xenobiotic Metabolism; abstracting; base; cell growth regulation; chemokine; cytokine; experience; high throughput technology; improved; prevent; receptor; rural area; size; tumor; virus genetics

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.

描述：基因-环境 EBV 相互作用在鼻咽癌病因学中的作用 摘要/摘要 我们的长期目标是为识别未分化鼻咽癌 (NPC) 高危人群以及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），几项规模较小、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，之前的研究还没有允许同时量化它们的作用，并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EB病毒株、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以及4号和5号染色体上候选基因的变异的主要影响； 2) 确定关键的基因-环境-EBV 相互作用。基于波士顿哈佛大学公共卫生学院、中国两个主要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 Fred Hutchinson 癌症中心的集体经验，并经过广泛的规划和试点研究，我们建议在世界上鼻咽癌发病率最高的中国南方两个省份开展一项基于人群的病例对照研究。我们将对总共 2000 例经组织病理学确诊的鼻咽癌病例和同等数量的人群对照进行面对面访谈，收集肿瘤组织和血液，并进行基因分型和其他实验室分析。根据拟议的大规模研究，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，相对风险低至 1.2，以及中等规模的相互作用。重要的是，我们还将开发一个包含组织、血清和 DNA 的生物库，可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可以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的程度。此外，高通量技术的最新改进现在使得进行大规模研究检查基因-环境-病毒相互作用成为可能。 NPC 叙述：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。这项研究将探讨中国南方地区鼻咽癌的遗传、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能力，以便早期发现鼻咽癌并成功治疗。