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

E Susan Amirian,Robert B Jenkins,Elizabeth B Claus,Ching C Lau,Michael E Scheurer,Francis Ali‐Osman,Sara H Olson,Melissa L Bondy,Siegal Sadetzki,Christopher I Amos,Renke Zhou,Faith G Davis,Sanjay Shete,Jonine L Bernstein,Rose Lai,Georgina Armstrong ,Daniel H Lachance ,Dora Il’yasova ,Margaret Wrensch ,Beatrice Melin ,Ryan Merrell ,Jill S Barnholtz‐Sloan ,Joellen M Schildkraut

doi:10.1002/cam4.682

Abstract

Varicella zoster virus (VZV) is a neurotropic α‐herpesvirus that causes chickenpox and establishes life‐long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case‐Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two‐stage random‐effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65–0.96). Furthermore, the protective effect of chickenpox was stronger for high‐grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta‐analyses of the literature and investigations of the potential biological mechanism, are warranted.

Highlights

Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox by initially infecting the respiratory mucosa and progressing into viremia, during which the virus is transported to and replicates in the skin [1]
Further stratifying by glioma diagnosis/study enrollment age group, we found that the strongest inverse association of chickenpox with high-grade glioma risk was observed among the youngest age group [data not shown]
A positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex

Summary

Introduction

Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox by initially infecting the respiratory mucosa and progressing into viremia, during which the virus is transported to and replicates in the skin [1]. The virus establishes life-long latency in the cranial nerve and dorsal root ganglia of the host, and may later reactivate in about 10–20% of VZV-infected individuals, causing shingles. Because of its neurotropism and its ability to establish decades-long latency across the neuraxis, [4] VZV is interesting to investigate in relation to gliomagenesis. 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]. 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]

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Conclusion