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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

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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.

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Acknowledgements

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

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Correspondence to Judith A Schwartzbaum.

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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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