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: 7690186
• 负责人: HANS-OLOV ADAMI
• 金额: $ 50.64万
• 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/7690186
• 关键词: Accounting; Age; Area; Beverages; 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; 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; Pilot Projects; Population Control; Predisposition; Preserved Foods; Production; Prophylactic treatment; Province; Public Health Schools; Relative Risks; Research; Research Personnel; Risk; Role; Secondary Prevention; Serum; Smoke; Smoking; Southeastern Asia; Susceptibility Gene; Testing; Tissue Banking; Tissue Banks; Tobacco smoke; Tumor Tissue; Undifferentiated; Variant; Vegetables; Virus; Virus Activation; Xenobiotic Metabolism; abstracting; base; cell growth regulation; chemokine; cytokine; experience; high risk; high throughput technology; improved; population based; prevent; receptor; rural area; 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：NPC摘要/摘要中的基因环境EBV相互作用我们的长期目标是为识别未分化的鼻咽癌（NPC）高风险的个体提供科学基础，并提高有效的初级和二级预防测量。在中国（NPC在某些地区是地方性的），几项较小的基于医院的研究表明，遗传易感性，爱泼斯坦 - 巴尔病毒（EBV）感染和其他环境因素在NPC的病因学中都很重要。但是，以前没有研究允许同时量化其角色，以及对它们之间的相互作用的详细分析。因此，我们的具体目的是1）确定a）特定EBV菌株的主要影响，b）饮食因素，c）吸烟和d）涉及致癌代谢，DNA修复，细胞受体和细胞因子的DNA修复，生产和调节的基因变化以及4和5染色体上的候选基因； 2）确定关键基因 - 环境-EBV相互作用。 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.总共有2,000例有组织病理学确认的NPC和相等数量的人口控制的事件，我们将进行面对面的访谈，收集肿瘤组织和血液，并进行基因分型和其他实验室分析。借助拟议的大型研究，我们将拥有足够的统计能力来检测遗传和环境暴露的主要影响，赋予相对风险低至1.2的相对风险以及中等大小的相互作用。重要的是，我们还将开发组织，血清和DNA的生物库，该库将用于其他研究人员以及未来的遗传研究。我们认为这项研究及时，因为最近中国机构的复杂性仅增加了，到城市和农村地区的大规模基于人群的分子流行病学研究变得可行。此外，现在的高通量技术的最新改进使得进行大规模研究研究基因环境 - 病毒相互作用是可行的。 NPC叙述：鼻咽癌（NPC）是东南亚最常见的癌症之一，但对其原因知之甚少。这项研究将检查中国南部NPC的遗传，病毒和环境风险因素，在中国南部，NPC率是世界上最高的。我们的目标是确定防止NPC的新方法，并改善对NPC的早期检测和成功治疗的高风险个体的识别。