High frequency of the H63D mutation of the hemochromatosis gene (HFE) in malignant gliomas

Abstract

Risk factors for brain tumors, except for ionizing radiations, remain substantially unknown.1 Iron exposure could be among these factors, as in vitro iron may promote the growth of malignant gliomas2 and iron chelators can inhibit this growth.3 Excess iron can favor the generation of highly reactive hydroxyl radicals, which, in turn, may cause point mutations in genomic DNA. Furthermore, increased levels of non-heme iron can convert nitric oxide from a proapoptotic to an antiapoptotic molecule. Notably, the c-myc oncogene, which is also expressed in high-grade gliomas, modulates the expression of genes controlling iron homeostasis, increasing the availability of intracellular iron.4 The hereditary hemochromatosis gene ( HFE ) has a critical role in iron homeostasis and two mutations of this gene, C282Y and H63D, are …