Dietary Selenium, Selenoenzyme Genes and Adult Glioma

描述（由申请人提供）：该提案是响应PAR-11-079（癌症预防研究小额赠款计划）提交的。神经胶质瘤是一种病因不明的致命的人类恶性肿瘤。本项目的目的是探索性研究硒（Se），一种与癌症和心血管疾病相关的必需微量矿物质，以及介导Se的主要细胞功能的硒蛋白的遗传变异与胶质瘤风险和生存的关系。硒的摄入量增加已被认为具有抗癌作用，通过细胞保护和氧化还原抗氧化功能，虽然还没有人口研究硒在胶质瘤中的作用。该项目将基于一项多中心NCI资助的（R 01 CA 116174）病例对照研究，该研究探索了美国东南部医疗中心正在进行的成人胶质瘤的遗传和环境风险因素。所有研究参与者都可以获得用于评估微量元素的指甲剪和用于遗传易感性研究的DNA。该项目的具体目标是：1）测量250例新发胶质瘤病例和250例匹配的社区对照者的趾甲Se i; 2）在大约1200例病例和1200例对照者中对硒酶的功能性或标记单核苷酸多态性（SNP）进行基因分型; 3）评估饮食Se和硒酶基因型与胶质瘤风险和患者预后的关系。据我们所知，这将是第一个研究膳食硒作为神经胶质瘤危险因素的研究。该项目还将首次对胶质瘤中硒酶的遗传变异进行全面评估。基于一项大型的、已完成的病例对照研究，该项目提供了关于潜在饮食风险因素、肿瘤发展机制和有前途的新研究领域的具有成本效益和及时的新信息。

DESCRIPTION (provided by applicant): The proposal is submitted in response to PAR-11-079 (Cancer Prevention Research Small Grant Program). Glioma is a lethal human malignancy of unknown etiology. The aims of this project are to conduct an exploratory investigation on the relationships of selenium (Se), an essential trace mineral linked to cancer and cardiovascular disease, and genetic variation in selenoproteins which mediate the major cellular functions of Se, with risk and survival in glioma. Increased intake of Se has been suggested to have anticarcinogenic effects through cellular protective and redox antioxidant functions, though no population study has yet examined the role of Se in glioma. The project will be based on a multicenter NCI-funded (R01 CA116174) case-control study exploring genetic and environmental risk factors for adult glioma underway at medical centers in the Southeastern US. Nail clippings for assessment of trace elements and DNA for study of genetic susceptibility are available for all study participants. Specific aims of this project are to: 1) Measure toenail Se i 250 incident glioma cases and 250 matched community controls; 2) Genotype functional or tagging single nucleotide polymorphisms (SNPs) in the selenoenzymes in approximately1200 cases and 1200 controls; and 3) Evaluate associations of dietary Se and selenoenzyme genotypes for relationships with glioma risk and patient outcome. To our knowledge, this will be the first study to investigate dietary Se as a glioma risk factor. The project will also provide th first comprehensive evaluation of genetic variation in selenoenzymes in glioma. Based on a large, completed case-control study, the project offers cost-effective and timely new information on a potential dietary risk factor, mechanisms for tumor development, and promising new areas for research.