GENETIC EPIDEMIOLOGY OF MALIGNANT GLIOMA

恶性胶质瘤的遗传流行病学

• 批准号: 2894845
• 负责人: MARGARET R. WRENSCH
• 金额: $ 69.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-15 至 2001-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2894845
• 关键词: antioxidants; cancer risk; carcinogens; clinical research; disease /disorder onset; family genetics; gender difference; genetic markers; genetic models; genetic polymorphism; glioma; human subject; immunocytochemistry; interview; medical records; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrition aspect of cancer; nutrition related tag; p53 gene /protein; pathogenic diet; questionnaires; smoking; tumor suppressor genes

DESCRIPTION: (Adapted from Applicant's Abstract). This is the second submission for the continuation of a case-control study of gliomas. The originally funded study focussed on questionnaire risk factors and segregation analysis, and the current plan is to continue case and control recruitment, and to broaden the work to include metabolic susceptibility polymorphisms. Although diverse familial and environmental risk factors have been implicated in this cancer, no dominant factors have yet emerged. Recent studies suggest etiologic heterogeneity, even within histologic types. The application builds on the assumption that tumor status for p53 may be used to define a more homogeneous subset of glioma. The application proposes to enroll 400 additional adult cases in 6 San Francisco counties, and 400 population-based controls obtained through random digit dialing, frequency matched to the cases on age, sex, and race. In-person interviews with an abbreviated version of the original questionnaire will request information on family and personal medical history, occupation, smoking, and other factors. Dietary assessment with food models with emphasize antioxidant consumption and potential carcinogenicity of foods. Blood will be collected from all willing subjects. Polymorphisms for glutathione sulfotransferases mu (GSTM1) and theta (GSTT), cytochromes p450 1A1 (CYP1A1) and 2D6 (CYP2D6), N-acetyl-transferase 2 (NAT2), and epoxide hydrolase (EPHX) will be determined for all new and 357 original subjects with blood specimens. Immunohistochemistry of astrocytic tumors will detect unusual accumulation of 53 kDa protein (p53); molecular methods will determine mutations in a defined subset. Analysis will address 4 aims: to 1) replicated preliminary findings of an association of GSTM1 deletion in women with an early onset; 2) test hypotheses that p53+ cases will be more likely than p53- cases to consume highly carcinogenic foods and less likely to consume antioxidants or be homozygously deleted for GSTM1; 3) compare frequencies of polymorphisms in other genes between p53+ and p53- cases; and 4) conduct exploratory analyses of other risk factors stratifying by genotype and p53 status of case tumors. High risk families will be ascertained to facilitate future linkage studies.

描述：（改编自申请人摘要）。 这是第二 提交继续进行神经胶质瘤病例对照研究。 的 最初资助的研究侧重于问卷调查的风险因素， 隔离分析，目前的计划是继续病例和控制 招募，并扩大工作，包括代谢易感性 多态性 尽管家庭和环境危险因素多种多样 与这种癌症有关，但尚未出现主导因素。 最近的研究表明病因异质性，即使在组织学 类型 该应用程序建立在假设p53的肿瘤状态 可用于定义胶质瘤的更同质的子集。 应用 建议在6个弗朗西斯科县再招募400例成人病例， 以及通过随机数字拨号获得的400个基于人群的对照， 频率与年龄、性别和种族的病例相匹配。 面对面访谈 与原始问卷的缩写版本将要求 家庭和个人病史、职业、吸烟和 其他因素 食物模型的膳食评估 抗氧化剂的消耗和潜在的致癌性的食物。 血液将 从所有自愿的受试者中收集。 谷胱甘肽的多态性 磺基转移酶mu（GSTM 1）和theta（GSTT），细胞色素p450 1A 1（CYP 1A 1） 和2D 6（CYP 2D 6）、N-乙酰基转移酶2（NAT 2）和环氧化物水解酶 将确定所有新受试者和357例原始受试者的EPHX， 标本 星形细胞肿瘤的免疫组化可以检测到 53 kDa蛋白（p53）的积累;分子方法将确定 在定义的子集中的突变。 分析将涉及4个目标：1） 女性GSTM 1缺失相关性的重复初步发现 早期发病; 2）检验假设，即p53+病例更有可能 比p53-病例消耗高致癌性食物， 消耗抗氧化剂或同源删除GSTM 1; 3）比较 p53+和p53-病例之间其他基因多态性的频率; 4)对其他风险因素进行探索性分析， 病例肿瘤的基因型和p53状态。 高风险家庭将 以便利今后的联系研究。