Abstract 1051: Association of Toxoplasma gondii antibodies in blood and risk of glioma
Authors: Hodge James M. , Coghill Anna E. , Kim Youngchul , Bender Noemi , Smith-Warner Stephanie , Grimsrud Tom K. , Gapstur Susan M. , Waterboer Tim , Teras Lauren R. , Egan Kathleen M. 
Published: September 2020

Abstract
Background: Brain and other nervous system cancers are relatively rare but remain the eighth most common cancer among persons aged 40 years and older. Gliomas are the most common type of primary brain cancer, have poor overall survival, and their etiology remains unclear. Toxoplasma gondii (T. gondii) is a common protozoan parasite and has been reported to cause glioma-like tumors in animals. In humans, the infection shows affinity to neural tissue and may lead to local necrosis and inflammation, and the formation of cysts in the brain from which infection may be reactivated according to host immunologic status. Previous ecologic and case-control studies have suggested an association with increased risk of gliomas in humans infected with T. gondii, but retrospective collection of exposure information from brain tumor patients is challenging. In this study, we assessed the relation between prediagnostic T. gondii antibodies and risk of glioma in two prospective cohorts.
Methods: Cases and matched controls were selected from the American Cancer Society's Cancer Prevention Study-II (CPSII) and the Norwegian Cancer Registry's Janus Serum Bank (Janus). To avoid potential effects of preclinical disease on serum antibody titers, the study was restricted to cases with blood collected a minimum of 3 years (in CPSII) or 5 years (in Janus) prior to glioma diagnosis. Using a multiplex serological assay, blood samples were analyzed simultaneously for antibodies to two surface antigens (p22 and sag1) specific to T. gondii which represent acute parasitic infection. Samples were considered positive for T. gondii infection if either antibody was positive, defined using assay-specific cutoffs unique to each antigen. Conditional logistic regression was used to calculate odds ratios for each cohort separately.
Results: A total of 37 cases and 74 controls were included from CPSII while 323 cases and 323 controls were included from Janus. The median age at blood draw was 71 years in CPSII and 41.1 years in Janus. In both cohorts, there was a suggestive increased risk of glioma among those infected with T. gondii. The association was strongest for gliomas diagnosed in approximately the first decade after blood collection in both Janus (OR: 2.50; 95% CI: 0.97-6.44, p = 0.058) and CPSII (OR: 2.71; 95% CI: 0.95-7.62, p = 0.060), with similar results observed in high grade glioblastoma (CPSII N = 27, OR: 2.31, 95% CI: 0.71-7.47; Janus N = 61, OR: 2.25, 95% CI: 0.70-7.31) and lower grade gliomas (Janus N = 47, OR: 3.00, 95% CI: 0.61-15).
Conclusions: Blood antibody levels from two prospective cohorts indicate a possible association between T. gondii infection and increased risk of glioma. The association was strongest in the first decade after antibody measurement. The consistency, magnitude, and direction of the association support the need for pooled analyses with larger case numbers for definitive investigation.
Citation Format: James M. Hodge, Anna E. Coghill, Youngchul Kim, Noemi Bender, Stephanie Smith-Warner, Tom K. Grimsrud, Susan M. Gapstur, Tim Waterboer, Lauren R. Teras, Kathleen M. Egan. Association of Toxoplasma gondii antibodies in blood and risk of glioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1051.