Southeast Region Case-Control Study of Adult Glioma

东南地区成人胶质瘤病例对照研究

• 批准号: 7198202
• 负责人: Kathleen M. Egan
• 金额: $ 87.32万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7198202
• 关键词: ABCB1 gene; ABCC1 gene; Adult; Adult Glioma; Age; Alcohol consumption; Alcohols; Aldehydes; Alkylating Agents; Animals; Ascorbic Acid; Base Excision Repairs; Basic Science; Beer; Blood - brain barrier anatomy; Brain; Brain Neoplasms; CYP2E1 gene; Carcinogens; Carrier Proteins; Case-Control Studies; Cessation of life; Characteristics; Chemotherapy-Oncologic Procedure; Clinic; Communities; Consumption; DNA; DNA Repair; Data; Descriptive Epidemiology; Development; Diagnosis; Diet; Diffuse; Disease; Enrollment; Ensure; Environmental Risk Factor; Epidemiology; Ethanol; Ethanol Metabolism; Etiology; Event; Exposure to; Food; Food Supplements; Frequencies; Funding; Future; GSTM1 gene; GSTP1 gene; GSTT1 gene; GSTT1 protein; Gender; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genome; Genotype; Glioma; Gliomagenesis; Guanine; Haplotypes; Human; Immunity; In Vitro; Incidence; Individual; Interview; Light; Link; MGMT gene; MLH1 gene; MSH2 gene; MSH3 gene; MSH6 gene; Malignant Neoplasms; Malignant neoplasm of brain; Measures; Meat; Medical History; Metabolism; Molecular Target; Molecular Weight; Morbidity - disease rate; Neurology; Nitrates; Nitrites; Nitro Compounds; Nitrosamines; Nitroso Compounds; Nucleotides; Numbers; Oral; PMS1 gene; PMS2 gene; POLB gene; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Play; Population; Population Control; Predisposition; Prevention; Process; Progress Review Group; Questionnaires; Recommendation; Recruitment Activity; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Sample Size; Sampling; Smoke; Smokeless Tobacco; Southeastern United States; Stomach; Structure; Subgroup; Susceptibility Gene; Testing; Tobacco; Toxin; Vitamin E; Week; XRCC1 gene; adduct; base; brain tissue; cancer genetics; case control; cytochrome P-450 CYP2A6 (human); day; design; environmental agent; gene environment interaction; glutathione S-transferase M1; glutathione S-transferase pi; human study; insight; loss of function; modifiable risk; neurosurgery; nitrate; novel; programs; relating to nervous system; repaired; reproductive; therapeutic target; treatment center; tumor

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.

描述（由申请人提供）：由大脑的非神经或神经胶质组织（“神经胶质瘤”）引起的肿瘤构成了最致命的人类癌症之一。很少进行神经胶质瘤的病例对照研究，并且肿瘤的病因在很大程度上尚不清楚。然而，该疾病的描述性流行病学，包括美国东南部的神经胶质瘤过多，与疾病中的环境成分一致。基于实验证据的强大候选危险因素包括在加工肉和烟草产品中接触N-硝基化合物（NOC）以及酒精的消费。为了阐明饮食，基因和其他潜在危险因素对成人神经胶质瘤的贡献，我们提出了一项基于诊所的，多机构的病例控制研究。具有新诊断神经胶质瘤的成年人将从美国东南部的5个治疗转介中心招募。通常在诊断后的几天或几周内，将直接从诊所招募受试者。在5年的项目中，估计有1,200人患有胶质瘤和年龄和性别匹配的社区控制。饮食的信息将使用经过验证的食品频率问卷收集，并补充了由Sinha和同事在NCI开发的问卷调查，专门针对饮食中的NOC和其他肉类致癌物。在结构化的访谈中，还将收集有关特应性免疫的数据，以及过去研究中与神经胶质瘤风险相关的其他暴露。为了探索遗传易感性的贡献，将从病例和对照组中收集口服DNA样品，并进行了整个基因组扩增，以增强DNA以进行计划和未来的基因分型。候选SNP和单倍型都将在31个涉及NOC代谢，DNA修复和致癌物进入中枢神经系统的敏感性基因中进行检查。有了大量用于分析的信息，该研究将有能力研究酒精消耗和与这些途径中易感基因的相互作用。拟议的研究将是美国最大的胶质瘤病例对照研究。该研究以高发病率区域为基础，可以确定新的环境风险因素，并为美国主要致命癌症提供有关预防和治疗的新见解。