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

描述（由申请人提供）：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，通常在诊断的第一年内死亡率为50%。除了职业、感染和环境因素可能参与脑癌的病因学之外，在基于人群的研究中也记录了与恶性胶质瘤，特别是多形性胶质母细胞瘤（GBM）遗传相关的证据。这项流行病学研究的目的是证实在旧金山弗朗西斯科海湾地区的一个队列中观察到的某些I类人类白细胞抗原（HLA）变体（等位基因和单倍型）与GBM的发生和进展有差异。拟议工作的目标是检查HLA和相关（邻近）多态性在一个新的队列的145 GBM患者和145对照组，1：1匹配的种族（欧洲裔美国人），性别，年龄组和居住县。将通过分子技术解析HLA I类区域中的三个基因（HLA-A、HLA-B和HLA-C）、HLA II类区域中的一个基因（HLA-DRB 1）和位于I类和II类基因座之间的另一个基因（云母）的等位基因变体，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类标记物是否可以通过来自新队列的数据来确认或细化。作为次要目的，将对100例间变性星形细胞瘤（成人脑癌的第二种最常见形式）患者和100例适当匹配的对照受试者（均为欧洲裔美国人）进行相同的分析，以评价基于GBM的结果的普遍性。总的来说，通过定义高度多态性的HLA I类分子的作用，这些分子对细胞毒性T淋巴细胞功能和自然杀伤细胞活性至关重要，这项研究将有助于阐明免疫监视和炎症在美国成人脑癌发病和预后中的重要性。这项基于人群的研究将检查与多形性胶质母细胞瘤遗传相关性的一致性，多形性胶质母细胞瘤是成人脑癌中最常见和最严重的形式。特别是，通过对精心挑选的人群的新数据和现有数据进行流行病学分析，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，并为进一步的合作研究铺平道路。

DESCRIPTION (provided by applicant): 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. 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.