Genetic Susceptibility and Brain Tumors

Polymorphisms in genes might modify the effects of exogenous and endogenous carcinogens in brain tumor development. We have evaluated the glutathione-S-transferase and cytochrome P-450 families of genes, both of which encode enzymes involved in the metabolism of solvents and other substrates. Occupational exposure to lead might cause meningioma, and a polymorphism in a gene for an enzyme that influences blood levels of lead [delta-aminolevulinic acid dehydratase, (ALAD)] was positively associated with the risk of meningioma. The association between glioma risk and history of allergies is being explored by examining the relation between glioma risk and polymorphisms in cytokine genes, and polymorphisms in a large panel of genes related to innate immunity also are under study. A recent paper from this study concerning apoptosis and cell cycle control genes identified caspase 8 as a possible susceptibility gene. Analyses concerning polymorphisms in oxidative stress genes, DNA repair genes, and insulin-like growth factor genes are in progress.

No single epidemiological study of brain tumors has adequate statistical power to evaluate most gene-environment or gene-gene interactions. An international consortium of brain tumor epidemiological studies (BTEC) was organized so that brain tumor risks associated with genetic susceptibility and specific exposures can be evaluated in the combined studies. .