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

项目摘要 成人脑癌(主要是胶质瘤)是人类最严重的恶性肿瘤，通常有50% 确诊第一年内的病死率。除了可能涉及职业性、传染性和 脑癌病因学中的环境因素，恶性胶质瘤遗传关联的证据， 尤其是多形性胶质母细胞瘤(GBM)，在人群研究中也得到了证实。这个 这项流行病学研究计划的目的是确认来自旧金山的队列观察结果。 旧金山湾区某些人类I类白细胞抗原变异体(等位基因和单倍型)可以 与肾小球基底膜的发生和发展有不同的相关性。拟议工作的目标是检查 145名GBM患者和145名对照组的新队列中的HL A及其相关(邻近)基因多态性， 按种族(欧洲裔美国人)、性别、年龄组和居住县1：1匹配。等位基因 人类白细胞抗原I区3个基因(A、B、C)和1个基因(DRB1)的变异 第II类区域和位于第I类和第II类基因座之间的另一个(MICA)区域将由分子解析 在本研究人群中促进流行病学分析的技术。其主要目标是确定是否 以前确定的人类白细胞抗原I类标记物可以通过新队列的数据来确认或改进。作为一名 第二个目标，相同的分析将扩展到100名间变性星形细胞瘤患者(第二个 最常见的成人脑癌)和100名匹配正常的对照组(均为欧洲人 美国人)，以评估基于GBM的结论的普适性。总体而言，通过定义 高度多态的人类白细胞抗原I类分子对细胞毒T淋巴细胞功能和天然的 杀伤细胞活性，这项研究将有助于阐明免疫监测和炎症在 美国成人脑癌的发病和预后。项目叙事 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， 这是成人脑癌最常见、最严重的形式。特别是通过流行病学 对精心挑选的人群的新数据和现有数据进行分析，这项工作的目的是确认和 人类白细胞抗原(HL A)基因分型与成人脑癌关系的研究 进一步的合作研究。

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.