Abstract
BACKGROUND: Previous epidemiological studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. METHODS: We conducted a case-control study using participants from the University of California San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory, and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free control individuals (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. RESULTS: Elevated total IgE was associated with reduced risk of IDH wild-type glioma (risk ratio [RR] = 0.78, 95% CI = 0.71 to 0.86) and IDH-mutant glioma (RR = 0.73, 95% CI = 0.63 to 0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH wild-type glioma (RR = 0.79, 95% CI = 0.67 to 0.93). The reduction in mortality risk was statistically significant in female individuals only (RR = 0.75, 95% CI = 0.57 to 0.98), with an improvement in median survival of 6.9 months (P < .001). CONCLUSION: Elevated serum IgE was associated with improved prognosis for IDH wild-type glioma, with a more pronounced protective effect in female than male individuals, which has implications for the future study of IgE-based immunotherapies for glioma.