Southeast Region Case-Control Study of Adult Glioma

描述(申请人提供)：源于大脑的非神经或神经胶质组织的肿瘤(胶质瘤)构成了人类最致命的癌症之一。很少有神经胶质瘤的病例对照研究，肿瘤的病因很大程度上是未知的。然而，这种疾病的描述性流行病学，包括美国东南部原因不明的过度胶质瘤，与疾病的环境因素是一致的。根据实验证据，强烈的候选风险因素包括接触加工肉类和烟草产品中的N-亚硝基化合物(NOCs)，以及饮酒。为了阐明饮食、基因和其他潜在危险因素对成人胶质瘤的影响，我们建议进行一项以临床为基础的、多机构的病例对照研究。新诊断为胶质瘤的成年人将从美国东南部的5个治疗转诊中心招募。受试者将直接从诊所登记，通常在确诊后几天或几周内。在这项为期5年的项目中，估计有1200名脑胶质瘤事件患者以及年龄和性别匹配的社区控制人员将参加这项研究。关于饮食的信息将使用经过验证的食物频率问卷收集，并辅之以由NCI的Sinha和同事开发的问卷，该问卷专门用于测量饮食中的NOC和其他肉类致癌物质。在结构化采访中，还将收集有关特应性免疫和过去研究中与胶质瘤风险有关的其他暴露的数据。为了探索遗传易感性的贡献，将从病例和对照中收集口腔DNA样本，并进行全基因组扩增，以增加DNA，为计划和未来的基因分型做准备。候选SNPs和单倍型都将在一组31个拟议的易感基因中进行检测，这些基因涉及NOC新陈代谢、DNA修复和致癌物进入中枢神经系统。有了大量可供分析的数据，这项研究将有能力调查酒精消费和NOC暴露与这些途径中的易感基因的相互作用。这项拟议的研究将是美国最大的胶质瘤病例对照研究。这项研究以高发地区为基础，可能会识别新的环境风险因素，并为预防和治疗美国一种主要的致命癌症提供新的见解。

DESCRIPTION (provided by applicant): Tumors arising from non-neural or glial tissue of the brain ('gliomas') constitute one of the most lethal human cancers. Few case-control studies of glioma have been undertaken, and the etiology of the tumor is largely unknown. However, the descriptive epidemiology of the disease, including an unexplained excess of glioma n the southeastern US, is consistent with an environmental component in the disease. Strong candidate risk factors, based on experimental evidence, include exposure to N-nitroso compounds (NOCs) in processed meats, and tobacco products, and consumption of alcohol. To shed light on the contribution of diet, genes and other potential risk factors to adult glioma, we are proposing a clinic-based, multi-institutional case- control study. Adults with a new diagnosis of glioma will be recruited from 5 treatment referral centers in the southeastern US. Subjects will be enrolled directly from clinics, generally within days or weeks of diagnosis. In the 5-year project, an estimated 1,200 persons with incident glioma and age- and gender-matched community controls will be enrolled in the study. Information on diet will be collected using a validated food frequency questionnaire, supplemented with a questionnaire developed by Sinha and colleagues at NCI designed specifically to measure NOCs and other meat carcinogens in the diet. In a structured interview, data will also be gathered on atopic immunity, and other exposures linked in past studies to glioma risk. To explore the contribution of genetic susceptibility, oral DNA samples will be collected from cases and controls, and whole genome amplification undertaken to augment the DNA for planned and future genotyping. Both candidate SNPs and haplotypes will be examined in a set of 31 proposed susceptibility genes involved in NOC metabolism, DNA repair and access of carcinogens to the CNS. With the large numbers available for analysis, the study will have power to investigate interactions of alcohol consumption and NOC exposure with the susceptibility genes in these pathways. The proposed study will be the largest US case-control study of glioma. Based in a high incidence region, the study may identify novel environmental risk factors and offer new insights on prevention and treatment for a leading fatal cancer in the US.