Human herpesvirus 6 (HHV-6) is a highly neurotropic beta-herpesvirus with demonstrated transformative properties. HHV-6 infection has been implicated in the etiologies of cancers, including lymphoma and leukemia; conditions with brain involvement, including epilepsy and encephalitis; and other disorders. HHV-6 is also the only human herpesvirus that has been proven to integrate into the chromosomes of a proportion (1-12%) of infected individuals. Because several traditional genetic association studies have failed to identify a variant that can account for the established relationship between family history and glioma risk, the possibility that chromosomally-integrated HHV-6 (CI-HHV-6), as a heritable factor, may explain a proportion of familial glioma cases warrants evaluation. To test this hypothesis, the prevalence of CI-HHV-6 in familial glioma cases and related and unrelated cancer-free control groups should be compared. Among glioma-affected families, the inheritance pattern of CI-HHV-6 could be evaluated by constructing pedigrees. If CI-HHV-6 is found to be associated with familial glioma risk, this knowledge could potentially lead to the future development of novel therapeutic and preventive approaches, including vaccines and immunotherapies targeted at the HHV-6 sequences.
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