Dietary Selenium, Selenoenzyme Genes and Adult Glioma

描述（由申请人提供）：该提案是根据PAR-11-079（癌症预防研究小额资助计划）提交的。胶质瘤是一种病因不明的致死性人类恶性肿瘤。本项目的目的是探索性研究与癌症和心血管疾病相关的必需微量矿物质硒（Se），以及介导硒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。增加硒的摄入被认为通过细胞保护和氧化还原抗氧化功能具有抗癌作用，尽管尚未有人群研究检查硒在胶质瘤中的作用。该项目将基于nci资助的一项多中心病例对照研究（R01 CA116174），该研究正在美国东南部的医学中心探索成人胶质瘤的遗传和环境风险因素。所有研究参与者均可获得用于微量元素评估的指甲剪报和用于遗传易感性研究的DNA。该项目的具体目的是：1)测量250例神经胶质瘤病例和250例匹配的社区对照；2)约1200例和1200例对照的硒酶基因型功能或标记单核苷酸多态性（snp）；3)评估膳食硒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风险因素的研究。该项目还将首次全面评估神经胶质瘤中硒酶的遗传变异。该项目基于一项已完成的大型病例对照研究，为潜在的饮食风险因素、肿瘤发展机制和有前景的新研究领域提供了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.