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

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.

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study

“…Due to differences in infrastructure, resources, and institutional policies, different types of controls and questionnaire administration methods had to be used across sites. However, we conducted a series of sensitivity analyses [detailed in (34)] to ensure that control type or questionnaire administration method did not discernably bias the results presented here. Nonetheless, we are unsure why the site-specific OR from UCSF demonstrates a significant adverse association between respiratory allergies and glioma here, as previous UCSF studies have reported inverse associations similar to those observed at our other sites (11, 20, 42).…”

“…Detailed information on the GICC study can be found elsewhere (34). Briefly, the GICC is an international consortium with 14 recruitment sites across five countries: Brigham and Women’s Hospital (MA, USA), Case Western Reserve University (Ohio, USA), Columbia University (NY, USA), Danish Cancer Society Research Centre (Copenhagen, Denmark), The Gertner Institute (Tel Hashomer, Israel), Duke University (NC, USA), University of Texas MD Anderson Cancer Center (TX, USA), Memorial Sloan Kettering Cancer Center (NY, USA), Mayo Clinic (MN, USA), NorthShore HealthSystem ( IL, USA), Umeå University (Umeå, Sweden), University of California, San Francisco (CA, USA), University of Southern California (CA, USA) and The Institute of Cancer Research (London, United Kingdom).…”

“…Data were stored in a centralized database. More information on data collection and reliability is provided elsewhere (34). …”

“…The overall GICC analysis plan (including sensitivity analyses) and a table of population demographics by study site has previously been published (34). For the current analyses, we compared cases and controls on relevant characteristics, overall, by study site, and by tumor grade (high-grade: WHO Grade IV; lower-grade: Grade II and III) among cases.…”

“…Two-stage random-effects restricted maximum likelihood (REML) modeling was used to aggregate estimates across study sites into overall meta-analysis ORs (mORs) (34). For each REML model, the I 2 statistic was calculated to assess the percentage of variability in the effect estimates due to heterogeneity, rather than sampling error.…”