The epidemiology of glioma in adults: a "state of the science" review

Abstract

Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults.

Inhibition of oxidative metabolism leads to p53 genetic inactivation and transformation in neural stem cells

“…In contrast, in progenitor/stem cells within the adult brain, which are less exposed to environmental insults, the initial event might be a metabolic defect, such as alterations of mitochondrial respiration. In fact, with the exception of exposure to ionizing radiations, a strong correlation between brain tumors and exposure to environmental carcinogens was never clearly demonstrated (45,46). It is important to note that there is lack of evidence that hereditary diseases carrying mutations in nuclear DNA and mtDNA-encoded mitochondrial factors, such as TK2, display increased cancer susceptibility.…”

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

“…No statistically significant associations were found between the TT and the CC genotypes (p-value = 0.866). Tick marks indicate censored data in cancer, but epidemiological studies evaluating tumor susceptibility conferred by genetic polymorphisms in its locus have not been extensively assessed [18][19][20][21][22]. Indeed, to the best of our knowledge, the current study is the first to evaluate associations between HOTAIR SNPs (rs920778 and rs12826786) and glioma susceptibility and prognosis.…”

“…Other putative causes may include familial aggregation, genetic syndromes, telomere maintenance and genetic polymorphisms [12][13][14]. The importance of inherited genetic variants in glioma risk has been highly addressed in both candidate-gene and genomewide association studies (GWAS) approaches, which revealed single nucleotide polymorphisms (SNPs) in cancer-related genes associated with glioma risk (e.g., TERT, EGF, EGFR, TGF-β1, CCDC26, CDKN2A/CDKN2B, PHLDB1 and RTEL1 [15][16][17][18]). …”

Concurrent chemoradiotherapy versus radiotherapy alone for “biopsy‐only” glioblastoma multiforme

“…1,2 Optimal treatment for GBM presently consists of maximal safe surgical resection followed by concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy.…”