Abstract
Gliomas account for almost 80% of primary malignant brain tumors, and they result in more years of life lost than do any other tumors. Glioblastoma, the most common type of glioma, is associated with very poor survival, so glioma epidemiology has focused on identifying factors that can be modified to prevent this disease. Only two relatively rare factors have so far been conclusively shown to affect glioma risk—exposure to high doses of ionizing radiation, and inherited mutations of highly penetrant genes associated with rare syndromes. In addition, preliminary evidence points to a lower glioma risk among people with allergic conditions and high levels of serum IgE. Recent research has focused on identifying germline polymorphisms associated with risk of glioma, and using molecular markers to classify glial tumors into more-homogenous groups. Because gene products probably interact with environmental factors or developmental signals to produce gliomas, large studies are needed to analyze associations between polymorphisms and glioma. Cohort studies of immune factors and glioma risk are being undertaken to validate the results of case–control studies. Studies of polymorphisms of genetic pathways with strong prior hypotheses are being planned, and whole-genome scans are being proposed to study high-risk families and case–control series. The Brain Tumor Epidemiology Consortium has been formed to co-ordinate these studies.
Key Points
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Only rare familial syndromes and exposure to high therapeutic doses of ionizing radiation are known causes of glioma
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Asthma and other allergic conditions decrease glioma risk, and this protective association has been confirmed for glioblastoma by objective evidence from asthma-related germline polymorphisms
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The general absence of consistent findings of associations between DNA repair and cell cycle regulation polymorphisms and glioma risk might be attributable to unexamined interactions between these genes and immune regulatory genes or with as yet unknown environmental factors or both
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References
Central Brain Tumor Registry of the United States [http://www.CBTRUS.org]
Kleihues P and Cavenee WK (1997) Tumors of the central nervous system: pathology and genetics. Lyon, France: International Agency for Research on Cancer
Davis FG et al. (1997) The rationale for standardized registration and reporting of brain and central nervous system tumors in population-based cancer registries. Neuroepidemiology 16: 308–316
Helseth A (1995) The incidence of primary central nervous system neoplasms before and after computerized tomography availability. J Neurosurg 83: 999–1003
Legler JM et al. (1999) Cancer surveillance series [corrected]: brain and other central nervous system cancers: recent trends in incidence and mortality. J Natl Cancer Inst 91: 1382–1390
Smith MA et al. (1998) Trends in reported incidence of primary malignant brain tumors in children in the United States. J Natl Cancer Inst 90: 1269–1277
Wrensch M et al. (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro-oncol 4: 278–299
Inskip PD et al. (1995) Etiology of brain tumors in adults. Epidemiol Rev 17: 382–414
Ichimura K et al. (2004) Molecular pathogenesis of astrocytic tumours. J Neurooncol 70: 137–160
Ohgaki H et al. (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64: 6892–6899
Preston-Martin S and Mack WJ (1996) Neoplasms of the nervous system. In Cancer Epidemiology and Prevention, 1231–1281 (Eds Schottenfeld D and Fraumeni JF) New York: Oxford University Press
Claus EB et al. (2005) Epidemiology of intracranial meningioma. Neurosurgery 57: 1088–1095
Edick MJ et al. (2005) Lymphoid gene expression as a predictor of risk of secondary brain tumors. Genes Chromosomes Cancer 42: 107–116
Ohgaki H and Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol (Berl) 109: 93–108
Relling MV et al. (1999) High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet 354: 34–39
Chen H et al. (2002) Diet and risk of adult glioma in eastern Nebraska, United States. Cancer Causes Control 13: 647–655
Cobbs CS et al. (2003) Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells. Cancer Res 63: 8670–8673
Gurney JG et al. (2002) Null association between frequency of cured meat consumption and methylvaline and ethylvaline hemoglobin adduct levels: the N-nitroso brain cancer hypothesis. Cancer Epidemiol Biomarkers Prev 11: 421–422
Huncharek M et al. (2003) Dietary cured meat and the risk of adult glioma: a meta-analysis of nine observational studies. J Environ Pathol Toxicol Oncol 22: 129–137
Krishnan G et al. (2003) Occupation and adult gliomas in the San Francisco Bay Area. J Occup Environ Med 45: 639–647
Maekawa A and Mitsumori K (1990) Spontaneous occurrence and chemical induction of neurogenic tumors in rats—influence of host factors and specificity of chemical structure. Crit Rev Toxicol 20: 287–310
Navas-Acien A et al. (2002) Occupation, exposure to chemicals and risk of gliomas and meningiomas in Sweden. Am J Ind Med 42: 214–227
Peterson DL et al. (1994) Animal models for brain tumors: historical perspectives and future directions. J Neurosurg 80: 865–876
Tedeschi-Blok N et al. (2001) Dietary calcium consumption and astrocytic glioma: the San Francisco Bay Area Adult Glioma Study, 1991–1995. Nutr Cancer 39: 196–203
Zheng T et al. (2001) Occupational risk factors for brain cancer: a population-based case–control study in Iowa. J Occup Environ Med 43: 317–324
Wacholder S et al. (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96: 434–442
Gobbel GT et al. (1998) Response of postmitotic neurons to X-irradiation: implications for the role of DNA damage in neuronal apoptosis. J Neurosci 18: 147–155
Silasi G et al. (2004) Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females. Biochem Biophys Res Commun 325: 1223–1235
Watts LT et al. (2005) Astrocytes protect neurons from ethanol-induced oxidative stress and apoptotic death. J Neurosci Res 80: 655–666
McGlynn KA et al. (1995) Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. Proc Natl Acad Sci USA 92: 2384–2387
El-Zein R et al. (2002) Epidemiology of brain tumors. In Cancer in the Nervous System, 2nd Edition, 252–266 (Ed. Levin VA) New York: Oxford University Press
Bondy M et al. (1994) Genetics of primary brain tumors: a review. J Neurooncol 18: 69–81
Wrensch M et al. (1997) Familial and personal medical history of cancer and nervous system conditions among adults with glioma and controls. Am J Epidemiol 145: 581–593
Grossman SA et al. (1999) Central nervous system cancers in first-degree relatives and spouses. Cancer Invest 17: 299–308
de Andrade M et al. (2001) Segregation analysis of cancer in families of glioma patients. Genet Epidemiol 20: 258–270
Malmer B et al. (2001) Genetic epidemiology of glioma. Br J Cancer 84: 429–434
Paunu N et al. (2002) A novel low-penetrance locus for familial glioma at 15q23–q26.3. Cancer Res 62: 3798–3802
Brenner AV et al. (2002) History of allergies and autoimmune diseases and risk of brain tumors in adults. Int J Cancer 99: 252–259
Schlehofer B et al. (1992) Medical risk factors and the development of brain tumors. Cancer 69: 2541–2547
Schlehofer B et al. (1999) Role of medical history in brain tumour development: results from the international adult brain tumour study. Int J Cancer 82: 155–160
Schwartzbaum J et al. (2005) Polymorphisms associated with asthma are inversely related to glioblastoma multiforme. Cancer Res 65: 6459–6465
Schwartzbaum J et al. (2003) Cohort studies of association between self-reported allergic conditions, immune-related diagnoses and glioma and meningioma risk. Int J Cancer 106: 423–428
Wiemels JL et al. (2004) Reduced immunoglobulin E and allergy among adults with glioma compared with controls. Cancer Res 64: 8468–8473
Wiemels JL et al. (2002) History of allergies among adults with glioma and controls. Int J Cancer 98: 609–615
Wrensch M et al. (2001) Prevalence of antibodies to four herpesviruses among adults with glioma and controls. Am J Epidemiol 154: 161–165
Wrensch M et al. (2005) History of chickenpox and shingles and prevalence of antibodies to varicella-zoster virus and three other herpesviruses among adults with glioma and controls. Am J Epidemiol 161: 1–10
Wrensch M et al. (2006) Serum IgE, tumor epidermal growth factor receptor expression, and inherited polymorphisms associated with glioma survival. Cancer Res 66: 4531–4541
Tang J et al. (2005) Positive and negative associations of human leukocyte antigen variants with the onset and prognosis of adult glioblastoma multiforme. Cancer Epidemiol Biomarkers Prev 14: 2040–2044
Berwick M and Vineis P (2000) Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 92: 874–897
Mohrenweiser HW et al. (2003) Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes. Mutat Res 526: 93–125
Wood RD et al. (2001) Human DNA repair genes. Science 291: 1284–1289
Goode EL et al. (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11: 1513–1530
Wang LE et al. (2004) Polymorphisms of DNA repair genes and risk of glioma. Cancer Res 64: 5560–5563
Wiencke J et al. (2005) Molecular features of adult glioma associated with patient race/ethnicity, age, and a polymorphism in O6-methylguanine-DNA-alkyltransferase. Cancer Epidemiol Biomarkers Prev 14: 1774–1783
Wrensch M et al. (2005) ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro-oncol 7: 495–507
Yang P et al. (2005) Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer 103: 2363–2372
Bond GL et al. (2004) A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 119: 591–602
Wrensch M et al. (2005) The molecular epidemiology of gliomas in adults. Neurosurg Focus 19: E5
Freije WA et al. (2004) Gene expression profiling of gliomas strongly predicts survival. Cancer Res 64: 6503–6510
Kleihues P and Ohgaki H (2000) Phenotype vs genotype in the evolution of astrocytic brain tumors. Toxicol Pathol 28: 164–170.
Lang FF et al. (1994) Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J Neurosurg 81: 427–436
Nigro JM et al. (2005) Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma. Cancer Res 65: 1678–1686
Rasheed BK et al. (1999) Molecular pathogenesis of malignant gliomas. Curr Opin Oncol 11: 162–167
Kleihues P et al. (1997) Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 150: 1–13
von Deimling A et al. (1995) Molecular pathways in the formation of gliomas. Glia 15: 328–338
Okada Y et al. (2003) Selection pressures of TP53 mutation and microenvironmental location influence epidermal growth factor receptor gene amplification in human glioblastomas. Cancer Res 63: 413–416
Schwartzbaum J et al. (2005) Prior hospitalization for epilepsy, diabetes, and stroke and subsequent glioma and meningioma risk. Cancer Epidemiol Biomarkers Prev 14: 643–650
James CD et al. (2002) Genetic and molecular basis of primary central nervous system tumors. In Cancer in the Nervous System, 239–251 (Ed. Levin VA) New York: Oxford University Press
National Center for Biotechnology Information [http://www.ncbi.nlm.nih.gov/entrez]
Acknowledgements
This work was supported by grants R03CA10337, RO1CA52689 and P50CA097257 from the National Institutes of Health.
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Schwartzbaum, J., Fisher, J., Aldape, K. et al. Epidemiology and molecular pathology of glioma. Nat Rev Neurol 2, 494–503 (2006). https://doi.org/10.1038/ncpneuro0289
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DOI: https://doi.org/10.1038/ncpneuro0289
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