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.