Interaction of allergy history and antibodies to specific varicella‐zoster virus proteins on glioma risk

Abstract

Glioma is the most common cancer of the central nervous system but with few confirmed risk factors. Glioma has been inversely associated with chicken pox, shingles, and seroreactivity to varicella virus (VZV), as well as to allergies and allergy-associated IgE. The role of antibody reactivity against individual VZV antigens has not been assessed. Ten VZV-related proteins, selected for high immunogenicity or known function, were synthesized and used as targets for antibody measurements in the sera of 143 glioma cases and 131 healthy controls selected from the San Francisco Bay Area Adult Glioma Study. Glioma cases exhibited significantly reduced seroreactivity compared to controls for six antigens, including proteins IE63 (OR = 0.26, 95%CI:0.12-0.58, comparing lowest quartile to highest), and the VZV-unique protein ORF2p (OR = 0.44, 95%CI:0.21-0.96, lowest quartile to highest). When stratifying the study population into those with low and high self-reported allergy history, VZV protein seroreactivity was only associated inversely with glioma among individuals self-reporting more than two allergies. The data provide insight into both allergy and VZV effects on glioma: strong anti-VZV reactions in highly allergic individuals is associated with reduced occurrence of glioma. This result suggests a role for specificity in the anti-VZV immunity in brain tumor suppression for both individual VZV antigens and in the fine-tuning of the immune response by allergy. Anti-VZV reactions may also be a biomarker of effective CNS immunosurveillance due to the tropism of the virus.

History of chickenpox in glioma risk: a report from the glioma international case–control study (GICC)

“…Findings from the previous literature, bolstered by those of our study, provide strong epidemiologic rationale for continued investigation of the potential role of chickenpox (or other manifestations of VZV infection) in glioma development [3,[8][9][10][11][12][13]. Future studies will need to account for the potential impact of the VZV vaccine, which was licensed in 1995 in the U.S. for use among children [2] (and therefore cannot be evaluated in the older population of the GICC).…”

“…The majority of published studies on VZV infection and glioma risk are from the San Francisco Bay Area Adult Glioma Study (SFBAGS) series [8][9][10][11]13]. Using both self-reported and serologic (anti-VZV IgG) data to assess history of chickenpox, findings from this series have indicated that prior exposure to VZV is associated with an approximately 40% lower glioma risk [9][10][11].…”

“…In fact, of the many viruses previously suspected to be involved in glioma susceptibility (i.e., simian virus 40, BK virus, JC virus, human cytomegalovirus, human herpesvirus-6) [5][6][7], VZV is the only virus consistently reported to have an inverse association with glioma [3]. The observed inverse relationship between VZV infection and glioma risk has remained relatively consistent across studies with different VZV exposure assessment methods, such as self-reported history of chickenpox [8,9], total anti-VZV Immunoglobulin G (IgG) levels [9][10][11][12], and levels of antibodies against specific VZV proteins [13]. Furthermore, because of its ability to replicate rapidly and lyse malignant glioma cells in vitro, VZV has even been proposed as a novel candidate for glioma virotherapy [14].…”

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

“…In animal models, pretreatment of GB with bortezomib has been shown to promote NK cell cytotoxicity and to inhibit tumor growth ultimately leading to prolonged survival [278]. Varicella zoster virus (VZV) is the only virus with negative correlation with GB [169,279]. NK cells represent a signi icant barrier to oncolytic herpes simplex virus therapy of GB [280].…”

Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors

“…Other risk factors that are not discussed here have been investigated in relation to glioma risk, including but not limited to: Type 1 and type 2 diabetes, body mass index, birth weight, hypertension, height, birth weight, menarche (age at onset), menopause (age at onset), coffee/caffeine consumption, low-density lipoprotein cholesterol, insulin-like growth factor 1, insulin-like growth factor binding protein, triglycerides, high-density lipoprotein cholesterol, pesticide exposure, extremely low frequency magnetic fields, vitamin E, A and C levels ( Preston-Martin and Mack, 1991 ; Kaplan et al, 1997 ; Houben et al, 2004 ; Linos et al, 2007 ; Holick et al, 2010 ; Kabat et al, 2011 ; Little et al, 2013 ; Malerba et al, 2013 ; Lee et al, 2014 ; Andersen et al, 2015 ; Li et al, 2015 ; Zhou et al, 2015 ; Seliger et al, 2016a , b ; Zhao et al, 2016 ; Wiedmann et al, 2017 ).…”