Hereditary disorders The exact causes of<unk> s are not known. Hereditary disorders such as neurofibromatoses (type 1 and type 2) and tuberous sclerosis complex are known to predispose to their development. Different oncogenes can cooperate in the development of<unk> s. Diet Some studies of diet and vitamin supplementation seem to indicate that dietary N-nitroso compounds might influence the risk of both childhood and adult brain tumors. Researchers have observed in some studies that brain tumor patients (or their mothers) have generally consumed more cured foods (also known as Curing) than control groups. Recently, Drs. Lee, Wrensch and others found that adults with<unk>  were more likely to consume diets high in cured foods and low in vitamin C-rich fruits and vegetables, and to consume diets high in nitrites and low in vitamin C. The effect was more pronounced in men than women. However, the pattern of increased risk with increased consumption of cured foods, and decreased risk with greater consumption of fruits, vegetables, and antioxidant vitamins is compatible with other cancer studies that show increased consumption of vegetables and possibly of fruits is associated with decreased cancer risk. Radiation A link between<unk> s and electromagnetic radiation from cell phones has not been conclusively proven. It was considered possible, though several large studies have found no conclusive evidence, as summarized by the NIH's National Cancer Institute review of the topic and its numerous citations, and the FCC. However, further research is still being pursued to obtain more robust evidence and verify that there is no relationship (the NIH's National Institute of Environmental Health Sciences most recent press release discussed an ongoing study showing mildly positive results, although it appears there may have been issues with the control group dying prematurely). Infection with cytomegalovirus Some studies have reported that glioblastomas are infected with cytomegalovirus, with suggestions that this may speed the development of tumors. However, this is a controversial opinion, with recent in-depth studies failing to find an association between viral infection and<unk>  growth. There is also evidence that previous studies may have been impacted by false-positive antibody staining artifacts. Other causes Though some studies have shown that farmers have higher rates of<unk> s compared to the general population, exposure to farm animals or manure is not associated with<unk> . Later studies have not found an association between farming and<unk> s; similar conflicting data concerns teachers and<unk> . More consistent data show that architects, surveyors, retail workers, butchers, and engineers have higher rates of<unk> s. Most studies have found that pesticide exposure is probably not a cause of<unk> , though a minority of studies have found an association. Inherited polymorphisms of the DNA repair genes Germ-line (inherited) polymorphisms of the DNA repair genes ERCC1, ERCC2 (XPD) and XRCC1 increase the risk of<unk> . This indicates that altered or deficient repair of DNA damage contributes to the formation of<unk> s. DNA damages are a likely major primary cause of progression to cancer in general. Excess DNA damages can give rise to mutations through translesion synthesis. Furthermore, incomplete DNA repair can give rise to epigenetic alterations or epimutations. Such mutations and epimutations may provide a cell with a proliferative advantage which can then, by a process of natural selection, lead to progression to cancer. Epigenetic repression of DNA repair genes is often found in progression to sporadic glioblastoma. For instance, methylation of the DNA repair gene MGMT promoter was observed in 51% to 66% of glioblastoma specimens. In addition, in some glioblastomas, the MGMT protein is deficient due to another type of epigenetic alteration. MGMT protein expression may also be reduced due to increased levels of a microRNA that inhibits the ability of the MGMT messenger RNA to produce the MGMT protein. Zhang et al. found, in the glioblastomas without methylated MGMT promoters, that the level of microRNA miR-181d is inversely correlated with protein expression of MGMT and that the direct target of miR-181d is the MGMT mRNA 3'UTR (the three prime untranslated region of MGMT messenger RNA). Epigenetic reductions in expression of another DNA repair protein, ERCC1, were found in an assortment of 32<unk> s. For 17 of the 32 (53%) of the<unk> s tested, ERCC1 protein expression was reduced or absent. In the case of 12<unk> s (37.5%) this reduction was due to methylation of the ERCC1 promoter. For the other 5<unk> s with reduced ERCC1 protein expression, the reduction could have been due to epigenetic alterations in microRNAs that affect ERCC1 expression. When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and such excess damages cause increased frequencies of mutation. Mutations in<unk> s frequently occur in either isocitrate dehydrogenase (IDH) 1 or 2 genes. One of these mutations (mostly in IDH1) occurs in about 80% of low grade<unk> s and secondary high-grade<unk> s. Wang et al. pointed out that IDH1 and IDH2 mutant cells produce an excess metabolic intermediate, 2-hydroxyglutarate, which binds to catalytic sites in key enzymes that are important in altering histone and DNA promoter methylation. Thus, mutations in IDH1 and IDH2 generate a "DNA CpG island methylator phenotype or CIMP" that causes promoter hypermethylation and concomitant silencing of tumor suppressor genes such as DNA repair genes MGMT and ERCC1. On the other hand, Cohen et al. and Molenaar et al. pointed out that mutations in IDH1 or IDH2 can cause increased oxidative stress. Increased oxidative damage to DNA could be mutagenic. This is supported by an increased number of DNA double-strand breaks in IDH1-mutated<unk>  cells. Thus, IDH1 or IDH2 mutations act as driver mutations in<unk>  carcinogenesis, though it is not clear by which role they are primarily acting. A study, involving 51 patients with brain<unk> s who had two or more biopsies over time, showed that mutation in the IDH1 gene occurred prior to the occurrence of a p53 mutation or a 1p/19q loss of heterozygosity, indicating that an IDH1 mutation is an early driver mutation.
Glioma
Gliosis
Glioblastoma
Astrocytoma
Meningioma
Malignant meningioma
Ameloblastoma
Coma