Etiology of Glioma and Glioblastoma

Abstract

Background: Although the incidence of glioma is low relative to other cancers, it ranks ninth overall in the United States for cancer-related death due to its high mortality. Accordingly, much research has focused on the identification of environmental and behavioral risk factors that may play a role in the incidence of glioma, with few notable results. Methods: We explored three factors that are possibly linked with risk of glioma: body habitus, tea and coffee intake, and statin use. We used data from three large, prospective cohort studies: the Nurses’ Health Study (NHS, n=121,700, begun in 1976), the Nurses’ Health Study II (NHSII, n=116,429, begun in 1989), and the Health Professionals Follow-Up Study (HPFS, n=51,529, begun in 1986), which together have accrued more than 550 glioma cases. Results: We demonstrated that whereas taller height was associated with increased risk of glioma (HR=1.07, 95%CI: 1.03-1.11 per 1 inch), adult BMI and waist circumference were not associated with risk. Higher tea intake was associated with lower risk of glioma (HR=0.73, 95%CI: 0.49-1.10, p-trend=0.05, comparing >2 cups/d to <1 cup/week), while caffeine intake and coffee intake were not associated with risk. In our analyses involving statin use, we identified substantial confounding by indication due to an unexpected inverse association between hyperlipidemia and glioma risk, which was attenuated in lagged analyses, suggesting reverse causation. After accounting for this confounding, statin use appeared to be associated with increased risk of glioma (HR=1.44, 95%CI: 1.10-1.87, comparing ever to never users). Conclusion: By identifying modifiable risk factors, it may be possible to enhance prevention and reduce incidence of glioma and glioblastoma, and also to improve our understanding of the pathogenesis of these tumors.