Southeast Region Case-Control Study of Adult Glioma

描述（由申请人提供）：由脑的非神经或神经胶质组织产生的肿瘤（“神经胶质瘤”）构成最致命的人类癌症之一。神经胶质瘤的病例对照研究很少，肿瘤的病因在很大程度上是未知的。然而，这种疾病的描述性流行病学，包括美国东南部不明原因的神经胶质瘤过多，与这种疾病的环境成分一致。根据实验证据，强有力的候选风险因素包括暴露于加工肉类和烟草制品中的N-亚硝基化合物（NOC）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，我们提出了一项基于临床的多机构病例对照研究。新诊断为神经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入组，通常在诊断后数天或数周内。在这项为期5年的项目中，估计有1,200名神经胶质瘤患者和年龄和性别匹配的社区对照者将参加这项研究。将使用经过验证的食物频率问卷收集有关饮食的信息，并补充由NCI的Sinha及其同事开发的问卷，该问卷专门用于测量饮食中的NOC和其他肉类致癌物。在结构化访谈中，还将收集关于特应性免疫和过去研究中与胶质瘤风险相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用于计划和未来的基因分型。候选SNP和单倍型将在一组涉及NOC代谢、DNA修复和致癌物进入CNS的31个拟议易感基因中进行检查。由于有大量数据可供分析，该研究将有能力调查酒精消费和NOC暴露与这些途径中易感基因的相互作用。这项研究将是美国最大的神经胶质瘤病例对照研究。基于高发地区，该研究可能会确定新的环境风险因素，并为美国主要致命癌症的预防和治疗提供新的见解。

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.