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The evidence for an association between a history of allergies and a reduced risk of glioma has been emerging (1). In this issue of the Journal, Calboli et al. (2) analyze associations between prediagnostic plasma immunoglobulin E (IgE) levels and the risk of adult glioma by combining data from four large prospective cohort studies. The pooled data resulted in a modest number of 169 glioma cases, but for a rare disease, this is a substantial contribution to the literature. A statistically significant protective association with borderline elevated levels of total IgE (25–100 kU/L) relative to clinically normal levels ( 100 kU/L) was not observed. The findings are somewhat perplexing, but further our understanding of the biological underpinnings of the protection that allergies appear to provide in the development of brain tumors. The results of Calboli et al. (2) are consistent with one other cohort study that reported a statistically significant inverse associ ation between risk of glioma and borderline elevated levels of IgE, but inconsistent associations with elevated IgE levels (3). This study (2) estimated an odds ratio (OR) near unity at elevated total IgE levels, whereas Schlehofer et al. (3) reported a protective association with elevated levels of respiratory allergen–specific IgE. They observed that the higher the level of respiratory allergen– specific IgE, the stronger was the association, and an increased association was statistically significant in patients with high grade glioma (3). Together, these studies point to an association between prediagnosis IgE level and risk of glioma, but the biological mechanism underlying this association is still unclear. The suggestion that allergies may be associated with a reduced risk of developing of brain tumors was made in the early 1990s (4). Since then, 10 case–control and two cohort studies have investigated this association using self-reported data on the history of allergic conditions. Results showed an inverse association of glioma risk with any allergic conditions compared with nonallergic conditions (pooled estimated OR = 0.60, 95% confidence interval [CI] = 0.52 to 0.69) (1). The association was statistically significant when limited to asthma, eczema, and hay fever as a group, and the association remained when consideration of proxy reporting was introduced in the analysis (1). These estimates based on self-report of allergies are similar to that observed by Calboli et al. (2) (total IgE 25–100 vs <25 kU/L, OR = 0.63, 95% CI = 0.42 to 0.93).

Allergies and Adult Gliomas: Cohort Results Strengthen Evidence for a Causal Association