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

描述(申请人提供)：成人脑癌(主要是胶质瘤)是人类最严重的恶性肿瘤，通常在诊断的第一年内死亡率为50%。除了职业性、感染性和环境性因素在脑癌病因中的潜在作用外，在基于人群的研究中，也有证据表明与恶性胶质瘤，特别是多形性胶质母细胞瘤(GBM)存在遗传关联。这项流行病学研究计划的目的是证实旧金山湾区的一个队列中的观察结果，即某些I类人类白细胞抗原(HL A)变异(等位基因和单倍型)可以与GBM的发生和发展有不同的相关性。这项拟议工作的目标是检查145名GBM患者和145名对照受试者的新队列中的人类白细胞抗原及其相关(邻近)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。位于人类白细胞抗原I类区域的3个基因(HLA-A、B和C)、位于II类区域的1个基因(HLA-DRB1)和位于I类和II类基因座之间的另一个基因(MICA)的等位基因变异将通过分子技术来解决，以便于在本研究人群中进行流行病学分析。主要目的是确定之前确定的人类白细胞抗原I类标志物是否可以通过新队列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名间变性星形细胞瘤患者(成人脑癌的第二种最常见形式)和100名匹配良好的对照组受试者(均为欧洲裔美国人)，以评估基于GBM的研究结果的概括性。总体而言，通过确定高度多态的HLAI类分子对细胞毒性T淋巴细胞功能和自然杀伤细胞活动至关重要的作用，这项研究将有助于阐明免疫监测和炎症在美国成人脑癌发生和预后中的重要性。这项基于人群的研究将检查多形性胶质母细胞瘤与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的和现有的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(HL A)基因与成人脑癌的关系，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.