Project Summary/Abstract The etiology of glioma, a rare, aggressive neoplasm that arises from the glial tissues of the brain, remains one of the least understood of human malignancies. Although incidence is relatively low, outcomes after diagnosis of glioma remain poor, especially for glioblastoma, the most lethal subtype. Although early identification of cases and rapid treatment is desirable, its low incidence makes population screening unfeasible. As a result, much research has focused on identifying risk factors for glioma that would allow for prevention efforts and risk stratification. Unfortunately, few environmental and behavioral risk factors for malignant brain tumors have been identified. Identification of novel risk factors has proved difficult for many reasons, including the rarity of glioma, its high mortality rate, and cognitive changes associated with these tumors that preclude accurate recall of exposure history by patients. Currently, exposure to ionizing radiation is the only confirmed, modifiable risk factor for these tumors. We propose to study three large, independent cohorts, the Nurses’ Health Study, Nurses’ Health Study II, and the Health Professionals Follow-Up Study, which together have followed more than 200,000 American adults since their establishment in 1976, 1989, and 1986, respectively. Together, 682 cases of glioma have been documented in these studies, with prospective follow-up via biennial questionnaires on dietary, behavioral, and environmental exposures. This project will evaluate three primary exposures: coffee and tea intake, use of aspirin and other non-steroidal anti- inflammatory drugs (NSAIDs), and use of statins, and subsequent risk of glioma. Each of these has pronounced antioxidant/anti-inflammatory properties, and have shown promise in other cancer sites. We believe that this work has strong potential to lead to identification of novel predictors of glioma risk, thereby refining our understanding of the etiology of these tumors, improving our ability to prevent their occurrence, and reducing the overall impact of glioma.