Glioma is an aggressive
neoplasm of the brain with poorly understood etiology. A limited number of pathogens have been examined as
glioma risk factors, but data from prospective studies with
infection status determined before disease are lacking. Herpesviruses comprise a large family of DNA viruses that infect humans and are linked to a range of
chronic diseases. We conducted a prospective evaluation of the association between antibody to six human herpesviruses and
glioma risk in the Janus Serum Bank (Janus) and the
Cancer Prevention Study-II (CPS-II). In Janus and CPS-II, the risk for
glioma was not related to seroprevalence of
herpes simplex virus-1, varicella zoster virus, or human herpes viruses 6A or 6B. In Janus, seropositivity to either the Epstein Barr virus (
EBV) EA[D] or VCAp18
antigen was associated with a lower risk of
glioma (
ORs: 0.55 [95% CI 0.32-0.94] and 0.57 [95% CI 0.38-0.85]). This inverse association was consistent by histologic subtype and was observed for
gliomas diagnosed up to two decades following antibody measurement. In Janus, seropositivity to at least one of three examined cytomegalovirus (CMV)
antigens (pp150, pp52, pp28) was associated with an increased risk of nonglioblastoma (OR: 2.08 [95% CI 1.07-4.03]). This association was limited to
tumors diagnosed within 12 years of antibody measurement. In summary, we report evidence of an inverse association between exposure to EBV and
glioma. We further report that CMV exposure may be related to a higher likelihood of the nonglioblastoma subtype.