GENETIC EPIDEMIOLOGY OF MALIGNANT GLIOMA

描述：(改编自申请人摘要)。这是第二次 提交继续进行胶质瘤病例对照研究的意见书。这个 最初资助的研究侧重于问卷风险因素和 隔离分析，目前的计划是继续病例和控制 招聘，并扩大工作范围，将代谢易感性包括在内 多态现象。尽管家庭和环境风险因素多种多样 都与这种癌症有牵连，目前还没有出现主导因素。 最近的研究表明，病原学上的异质性，甚至在组织学上也是如此 类型。该应用程序建立在假设肿瘤状态为p53的基础上 可以用来定义一个更均匀的胶质瘤亚群。应用程序 提议在旧金山的6个县额外招收400名成人病例， 以及通过随机数字拨号获得的400个基于人群的控件， 在年龄、性别和种族上与病例匹配的频率。面谈 原始调查问卷的缩写版本将要求 关于家庭和个人病史、职业、吸烟和 其他因素。饮食评估与食品模型的重点 食品的抗氧化剂消耗量和潜在致癌性。血肉之躯 从所有有意愿的受试者中收集。谷胱甘肽的多态现象 磺基转移酶Mu(GSTM1)和theta(GSTT)，细胞色素P450 1A1(CYP1A1) 和2D6(CYP2D6)、N-乙酰转移酶2(NAT2)和环氧化物水解酶 (EPHX)将测定所有新受试者和357名原始受试者的血液 标本。星形细胞肿瘤的免疫组织化学将检测异常 53 kDa蛋白(P53)的积累；分子方法将确定 定义的子集中的突变。分析将涉及4个目标：至1) 女性GSTM1缺失关联的重复初步研究结果 早期发病；2)检验假设，即P53+病例更有可能 比P53-病例食用高致癌食物的可能性更低 食用抗氧化剂或被GSTM1纯合子删除；3)比较 其他基因在P53+和P53-病例中的多态频率； 4)对其他风险因素进行探索性分析 病例肿瘤的基因分型和P53基因状态。高危家庭将是 为今后的连锁研究提供便利。

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.