Serially measured pre-diagnostic levels of serum cytokines and risk of brain cancer in active component military personnel

Background: There is growing evidence that history of allergic or autoimmune disease is associated with reduced risk of glioma, but few prospective studies have explored the biological basis. To assess associations with immune conditions and levels of 14 cytokines in serial prediagnostic serum samples, we conducted a study of glioma/brain cancer nested in a cohort of active component military personnel. Methods: A total of 457 case-control sets were ascertained from the Department of Defense (DoD) Automated Central Tumour Registry, Defense Medical Surveillance System (DMSS) database, and DoD Serum Repository. These were individually matched on sex, race/ethnicity, birth year, number of serum samples (1, 2 or 3), and date(s) of sample collection. We obtained diagnoses of pre-existing immune-related conditions from the DMSS database and measured cytokines using Meso Scale Discovery assays. Statistical analyses included conditional logistic regression. Results: Overall association between glioma and prior immune-related conditions was null. Higher levels of IL-15 and IL-16 were independently associated with lower glioma risks (P_trend = 0.002 and P_trend = 0.001); both associations were more pronounced in individuals with prior immune conditions (P_{heterogeneity} = 0.0009 and P_{heterogeneity} = 0.031). Conclusions: Associations with pre-diagnostic levels of IL-15 and IL-16 and their modification by diagnosis of immune-related conditions support the importance of immune alterations in glioma aetiology years before diagnosis.