Genetic Epidemiology of Adult Brain Cancer: A Follow-up Study

成人脑癌的遗传流行病学：一项后续研究

• 批准号: 7500868
• 负责人: Jianming Tang
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7500868
• 关键词: 6p21.3; Adult; Affect; Alleles; American; Anaplastic astrocytoma; Area; Astrocytoma; Chromosomes, Human, Pair 6; Class; County; Data; Diagnosis; Disease; Ethnic Origin; Etiology; European; Follow-Up Studies; Gender; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Glioblastoma; Glioma; Goals; HLA Antigens; Haplotypes; Human; Immune response; Immunologic Surveillance; Individual; Inflammation; Linkage Disequilibrium; Lymphocyte Function; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Mediating; Molecular; Natural Killer Cells; Occupational; Patients; Pattern; Plan B; Population; Population Study; Predisposition; Rate; Research; Role; San Francisco; Secondary to; T-Lymphocyte; Techniques; United States; Upper arm; Variant; Work; age group; base; cohort; cytotoxic; environmental agent; genetic association; genetic epidemiology; human leukocyte antigen gene; male; outcome forecast; residence

Project Summary Adult brain cancers (mostly gliomas) are the most severe forms of human malignancies, usually with a 50% fatality rate within the first year of diagnosis. Apart from potential involvement of occupational, infectious and environmental agents in the etiology of brain cancer, evidence for genetic associations with malignant glioma, especially glioblastoma multiforme (GBM), has also been documented in population-based studies. The objective of this epidemiological research initiative is to confirm observations in a cohort from the San Francisco Bay area that certain class I human leukocyte antigen (HLA) variants (alleles and haplotypes) can differentially correlate with the onset and progression of GBM. The goal of the proposed work is to examine HLA and related (neighboring) polymorphisms in a new cohort of 145 GBM patients and 145 control subjects, with 1:1 matching by ethnicity (European American), gender, age group and county of residence. Allelic variants of three genes (HLA-A, HLA-B and HLA-C) in the HLA class I region, one (HLA-DRB1) in the HLA class II region and another (MICA) located between class I and class II loci will be resolved by molecular techniques to facilitate epidemiological analyses in this study population. The primary aim is to determine if the previously identified HLA class I markers can be confirmed or refined by data from the new cohort. As a secondary aim, identical analyses will be extended to 100 patients with anaplastic astrocytoma (the second most common form of adult brain cancer) and 100 properly matched control subjects (all are European Americans) in order to evaluate the generalizability of findings based on GBM. Overall, by defining the role of highly polymorphic HLA class I molecules that are essential to cytotoxic T-lymphocyte function and natural killer cell activity, this study will help clarify the importance of immune surveillance and inflammation in the onset and prognosis of adult brain cancer in the United States. Project Narrative This population-based study will examine the consistency of genetic associations with glioblastoma multiforme, which is the most common and most severe form of adult brain cancer. In particular, through epidemiological analyses of new as well as existing data from carefully selected populations, this work aims to confirm and refine relationships of human leukocyte antigen (HLA) genotypes to adult brain cancer and to pave the way for further collaborative research.

项目摘要 成人脑癌（主要是神经胶质瘤）是人类恶性肿瘤中最严重的形式，通常有50% 确诊后第一年内的死亡率。除了可能涉及职业、传染和 脑癌病因学中的环境因素，与恶性神经胶质瘤遗传相关的证据， 尤其是多形性胶质母细胞瘤（GBM），也已经在基于人群的研究中被记录。的 这项流行病学研究的目的是证实在一个队列中的观察， 弗朗西斯科湾地区，某些I类人类白细胞抗原（HLA）变异体（等位基因和单倍型）可以 与GBM的发作和进展有差异性相关。拟议工作的目标是审查 HLA和相关（邻近）多态性在145例GBM患者和145例对照受试者的新队列中， 按种族（欧洲裔美国人）、性别、年龄组和居住县进行1：1匹配。等位基因 HLA I类区域中的三个基因（HLA-A、HLA-B和HLA-C）的变体，HLA I类区域中的一个（HLA-DRB 1）， II类区域和位于I类和II类基因座之间的另一个（云母）将通过分子生物学方法解析。 技术，以促进本研究人群的流行病学分析。主要目的是确定 先前鉴定的HLA I类标记物可以通过来自新组群的数据来确认或改进。作为 第二个目标，相同的分析将扩展到100例间变性星形细胞瘤患者（第二个 最常见的成人脑癌）和100名适当匹配的对照受试者（均为欧洲人 美国人），以评估基于GBM的发现的普遍性。总的来说，通过界定 高度多态性的HLA I类分子，其对于细胞毒性T淋巴细胞功能和天然的 这项研究将有助于阐明免疫监视和炎症在免疫系统中的重要性。 美国成人脑癌的发病和预后。项目叙述 这项基于人群的研究将检查多形性胶质母细胞瘤遗传相关性的一致性， 这是最常见和最严重的成人脑癌。特别是通过流行病学 通过对精心挑选的人群的新数据和现有数据进行分析，这项工作旨在确认和 完善人类白细胞抗原（HLA）基因型与成人脑癌的关系，并为 进一步合作研究。