Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Epidemiology and molecular pathology of glioma

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

  • Only rare familial syndromes and exposure to high therapeutic doses of ionizing radiation are known causes of glioma

  • 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

  • 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

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Glioma 2-year relative survival probabilities by age at diagnosis and histologic subtype, based on the follow-up of individuals diagnosed between 1973 and 2002.

References

  1. Central Brain Tumor Registry of the United States [http://www.CBTRUS.org]

  2. Kleihues P and Cavenee WK (1997) Tumors of the central nervous system: pathology and genetics. Lyon, France: International Agency for Research on Cancer

    Google Scholar 

  3. 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

    CAS  Article  Google Scholar 

  4. Helseth A (1995) The incidence of primary central nervous system neoplasms before and after computerized tomography availability. J Neurosurg 83: 999–1003

    CAS  Article  Google Scholar 

  5. 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

    CAS  Article  Google Scholar 

  6. 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

    CAS  Article  Google Scholar 

  7. Wrensch M et al. (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro-oncol 4: 278–299

    Article  Google Scholar 

  8. Inskip PD et al. (1995) Etiology of brain tumors in adults. Epidemiol Rev 17: 382–414

    CAS  Article  Google Scholar 

  9. Ichimura K et al. (2004) Molecular pathogenesis of astrocytic tumours. J Neurooncol 70: 137–160

    Article  Google Scholar 

  10. Ohgaki H et al. (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64: 6892–6899

    CAS  Article  Google Scholar 

  11. 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

    Google Scholar 

  12. Claus EB et al. (2005) Epidemiology of intracranial meningioma. Neurosurgery 57: 1088–1095

    Article  Google Scholar 

  13. Edick MJ et al. (2005) Lymphoid gene expression as a predictor of risk of secondary brain tumors. Genes Chromosomes Cancer 42: 107–116

    CAS  Article  Google Scholar 

  14. Ohgaki H and Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol (Berl) 109: 93–108

    Article  Google Scholar 

  15. Relling MV et al. (1999) High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet 354: 34–39

    CAS  Article  Google Scholar 

  16. Chen H et al. (2002) Diet and risk of adult glioma in eastern Nebraska, United States. Cancer Causes Control 13: 647–655

    Article  Google Scholar 

  17. 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

    CAS  PubMed  Google Scholar 

  18. 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

    PubMed  Google Scholar 

  19. 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

    CAS  PubMed  Google Scholar 

  20. Krishnan G et al. (2003) Occupation and adult gliomas in the San Francisco Bay Area. J Occup Environ Med 45: 639–647

    Article  Google Scholar 

  21. 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

    CAS  Article  Google Scholar 

  22. 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

    Article  Google Scholar 

  23. Peterson DL et al. (1994) Animal models for brain tumors: historical perspectives and future directions. J Neurosurg 80: 865–876

    CAS  Article  Google Scholar 

  24. 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

    CAS  Article  Google Scholar 

  25. 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

    CAS  Article  Google Scholar 

  26. 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

    Article  Google Scholar 

  27. 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

    CAS  Article  Google Scholar 

  28. 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

    CAS  Article  Google Scholar 

  29. Watts LT et al. (2005) Astrocytes protect neurons from ethanol-induced oxidative stress and apoptotic death. J Neurosci Res 80: 655–666

    CAS  Article  Google Scholar 

  30. 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

    CAS  Article  Google Scholar 

  31. 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

    Google Scholar 

  32. Bondy M et al. (1994) Genetics of primary brain tumors: a review. J Neurooncol 18: 69–81

    CAS  Article  Google Scholar 

  33. 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

    CAS  Article  Google Scholar 

  34. Grossman SA et al. (1999) Central nervous system cancers in first-degree relatives and spouses. Cancer Invest 17: 299–308

    CAS  Article  Google Scholar 

  35. de Andrade M et al. (2001) Segregation analysis of cancer in families of glioma patients. Genet Epidemiol 20: 258–270

    CAS  Article  Google Scholar 

  36. Malmer B et al. (2001) Genetic epidemiology of glioma. Br J Cancer 84: 429–434

    CAS  Article  Google Scholar 

  37. Paunu N et al. (2002) A novel low-penetrance locus for familial glioma at 15q23–q26.3. Cancer Res 62: 3798–3802

    CAS  PubMed  Google Scholar 

  38. Brenner AV et al. (2002) History of allergies and autoimmune diseases and risk of brain tumors in adults. Int J Cancer 99: 252–259

    CAS  Article  Google Scholar 

  39. Schlehofer B et al. (1992) Medical risk factors and the development of brain tumors. Cancer 69: 2541–2547

    CAS  Article  Google Scholar 

  40. 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

    CAS  Article  Google Scholar 

  41. Schwartzbaum J et al. (2005) Polymorphisms associated with asthma are inversely related to glioblastoma multiforme. Cancer Res 65: 6459–6465

    CAS  Article  Google Scholar 

  42. 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

    CAS  Article  Google Scholar 

  43. Wiemels JL et al. (2004) Reduced immunoglobulin E and allergy among adults with glioma compared with controls. Cancer Res 64: 8468–8473

    CAS  Article  Google Scholar 

  44. Wiemels JL et al. (2002) History of allergies among adults with glioma and controls. Int J Cancer 98: 609–615

    CAS  Article  Google Scholar 

  45. Wrensch M et al. (2001) Prevalence of antibodies to four herpesviruses among adults with glioma and controls. Am J Epidemiol 154: 161–165

    CAS  Article  Google Scholar 

  46. 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

    Article  Google Scholar 

  47. 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

    CAS  Article  Google Scholar 

  48. 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

    CAS  Article  Google Scholar 

  49. 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

    CAS  Article  Google Scholar 

  50. 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

    CAS  Article  Google Scholar 

  51. Wood RD et al. (2001) Human DNA repair genes. Science 291: 1284–1289

    CAS  Article  Google Scholar 

  52. Goode EL et al. (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11: 1513–1530

    CAS  PubMed  Google Scholar 

  53. Wang LE et al. (2004) Polymorphisms of DNA repair genes and risk of glioma. Cancer Res 64: 5560–5563

    CAS  Article  Google Scholar 

  54. 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

    CAS  Article  Google Scholar 

  55. Wrensch M et al. (2005) ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro-oncol 7: 495–507

    CAS  Article  Google Scholar 

  56. Yang P et al. (2005) Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer 103: 2363–2372

    CAS  Article  Google Scholar 

  57. 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

    CAS  Article  Google Scholar 

  58. Wrensch M et al. (2005) The molecular epidemiology of gliomas in adults. Neurosurg Focus 19: E5

    PubMed  Google Scholar 

  59. Freije WA et al. (2004) Gene expression profiling of gliomas strongly predicts survival. Cancer Res 64: 6503–6510

    CAS  Article  Google Scholar 

  60. Kleihues P and Ohgaki H (2000) Phenotype vs genotype in the evolution of astrocytic brain tumors. Toxicol Pathol 28: 164–170.

    CAS  Article  Google Scholar 

  61. 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

    CAS  Article  Google Scholar 

  62. 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

    CAS  Article  Google Scholar 

  63. Rasheed BK et al. (1999) Molecular pathogenesis of malignant gliomas. Curr Opin Oncol 11: 162–167

    CAS  Article  Google Scholar 

  64. Kleihues P et al. (1997) Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 150: 1–13

    CAS  PubMed  PubMed Central  Google Scholar 

  65. von Deimling A et al. (1995) Molecular pathways in the formation of gliomas. Glia 15: 328–338

    CAS  Article  Google Scholar 

  66. 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

    CAS  PubMed  Google Scholar 

  67. 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

    Article  Google Scholar 

  68. 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

    Google Scholar 

  69. National Center for Biotechnology Information [http://www.ncbi.nlm.nih.gov/entrez]

Download references

Acknowledgements

This work was supported by grants R03CA10337, RO1CA52689 and P50CA097257 from the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Judith A Schwartzbaum.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneuro0289

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing