Primary CNS tumors in adults and environmental factors: an update

View or download the full article: 
616-006.48; 614.1:614.71

S.G. Berntsson


Uppsala University Hospital, SE-751 85, Uppsala, Sweden


The incidence of adult primary brain tumors is increasing in some European countries.
High-dose ionizing irradiation, rare genetic syndromes, and genetic predisposition in 5 % of families are a few established environmental risk factors for brain tumor.
Mobile phone use that causes near brain exposure to radiofrequency electromagnetic waves and thus creates risks of CNS tumors has been the focus of many studies.
Nine meta-analyses were available on this subject. The Interphone multi-center case-control study is the largest one to date; it included 2.708 glioma and 2.409 meningioma cases and matched controls in 13 countries. Studies exploring metals (cadmium, lead), pesticides, outdoor pollution, virus, and risk of glioma created by exposure to them were reviewed.
Interphone study did not show increased risk of glioma or meningioma in mobile-phone users. One recent meta-analysis in 2017 found that prolonged exposure i.e.,> 10 years of all phone types was associated with increased risk of ipsilateral CNS tumor locations.
In another meta-analysis, long-term use of mobile-phones was found to be a risk factor for low-grade glioma. In case of all durations regarding mobile phone use and both sides of the head, the results of pooling data were more discordant. A large prospective study in
2014 showed that long term use vs never use increased risks of acoustic neurinoma (10+ years: RR = 2.46, 95 % CI = 1.07–5.64, P = 0.03), but not of glioma or meningioma. Studies of other risk factors showed no/weak/contradictory association with brain tumor risk.
In the absence of robust and consistent evidence, a causal relation between radiofrequency exposure and CNS tumors was not found. Large prospective studies of this kind regarding a disease with low incidence require a high number of participants and a long follow-up period.

brain tumor, glioma, meningioma, environmental risk factors.
Berntsson S.G. Primary CNS tumors in adults and environmental factors: an update. Health Risk Analysis, 2020, no. 3, pp. 176–181. DOI: 10.21668/health.risk/2020.3.21.eng
  1. Louis D.N., Perry A., Reifenberger G., Von Deimling A., Figarella-Branger D., Cavenee W.K., Ohgaki H. [et al.]. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol, 2016, vol. 131, no. 6, pp. 803–820. DOI: 10.1007/s00401-016-1545-1
  2. Ohgaki H., Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol, 2005, vol. 109, no. 1, pp. 93–108. DOI: 10.1007/s00401-005-0991-y
  3. Larjavaara S., Haapasalo H., Sankila R., Helen P., Auvinen A. Is the incidence of meningiomas underestimated? A regional survey. Br. J. Cancer, 2008, vol. 99, no. 1, pp. 182–184. DOI: 10.1038/sj.bjc.6604438
  4. Sughrue M.E., Rutkowski M.J., Aranda D., Barani I.J., McDermott M.W., Parsa A.T. Treatment decision making based on the published natural history and growth rate of small meningiomas. J. Neurosurg, 2010, vol. 113, no. 5, pp. 1036–1042. DOI: 10.3171/2010.3.JNS091966
  5. Lonn S., Klaeboe L., Hall P., Mathiesen T., Auvinen A., Christensen H.C., Johansen C., Salminen T. [et al.]. Incidence trends of adult primary intracerebral tumors in four Nordic countries. Int. J. Cancer, 2004, vol. 108, no. 3, pp. 450–455. DOI: 10.1002/ijc.11578
  6. Philips A., Henshaw D.L., Lamburn G., O'Carroll M.J. Brain Tumours: Rise in Glioblastoma Multiforme Incidence in England 1995–2015 Suggests an Adverse Environmental or Lifestyle Factor. J. Environ. Public. Health., 2018, vol. 2018, pp. 7910754. DOI: 10.1155/2018/7910754
  7. Ohgaki H., Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J. Neuropathol. Exp. Neurol., 2005, vol. 64, no. 6, pp. 479–489.
  8. Ron E., Modan B., Boice J.D. Jr., Alfandary E., Stovall M., Chetrit A., Katz L. Tumors of the brain and nervous system after radiotherapy in childhood. N. Engl. J. Med., 1988, vol. 20, no. 319 (16), pp. 1033–1039. DOI: 10.1056/NEJM198810203191601
  9. Shintani T., Hayakawa N., Kamada N. High incidence of meningioma in survivors of Hiroshima. Lancet, 1997, vol. 10, no. 349, pp. 1369. DOI: 10.1016/S0140-6736(05)63205-9
  10. Neglia J.P., Robison L.L., Stovall M., Liu Y., Packer R.J., Hammond S., Yasui Y., Kasper C.E. [et al.]. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J. Natl. Cancer. Inst., 2006, vol. 98, no. 21, pp. 1528–1537. DOI:10.1093/jnci/djj411
  11. Pearce M.S., Salotti J.A., Little M.P., McHugh K., Lee C., Kim K.P., Howe N.L., Ronckers C.M. [et al.]. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet, 2012, vol. 4, no. 380, pp. 499–505. DOI: 10.1016/S0140-6736(12)60815-0
  12. Cardis E., Richardson L., Deltour I., Armstrong B., Feychting M., Johansen C., Kilkenny M., McKinney P. [et al.]. The INTERPHONE study: design, epidemiological methods, and description of the study population. Eur. J. Epidemiol., 2007, vol. 22, no. 9, pp. 647–664. DOI: 10.1007/s10654-007-9152-z
  13. Group I.S. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international casecontrol study. Int. J. Epidemiol., 2010, vol. 39, no. 3, pp. 675–694. DOI: 10.1093/ije/dyq079
  14. Bortkiewicz A., Gadzicka E., Szymczak W.Mobile phone use and risk for intracranial tumors and salivary gland tumors – A meta-analysis. Int. J. Occup. Med. Environ. Health, 2017, vol. 30, no. 1, pp. 27–43. DOI: 10.13075/ijomeh.1896.00802
  15. Yang M., Guo W., Yang C., Tang J., Huang Q., Feng S., Jiang A., Xu X., Jiang G. Mobile phone use and glioma risk: A systematic review and meta-analysis. PLoS One, 2017, vol. 12, no. 5, pp. e0175136. DOI: 10.1371/journal.pone.0175136
  16. Benson V.S., Pirie K., Schuz J., Reeves G.K., Beral V., Green J. Million Women Study C. Mobile phone use and risk of brain neoplasms and other cancers: prospective study. Int. J. Epidemiol, 2013, vol. 42, no. 3, pp. 792–802. DOI: 10.1093/ije/dyt072
  17. Dubrow R., Darefsky A.S., Park Y., Mayne S.T., Moore S.C., Kilfoy B., Cross A.J., Sinha R. [et al.]. Dietary components related to N-nitroso compound formation: a prospective study of adult glioma. Cancer Epidemiol Biomarkers Prev, 2010, vol. 19, no. 7, pp. 1709–1722. DOI: 10.1158/1055-9965.EPI-10-0225
  18. Michaud D.S., Holick C.N., Batchelor T.T., Giovannucci E., Hunter D.J. Prospective study of meat intake and dietary nitrates, nitrites, and nitrosamines and risk of adult glioma. Am. J. Clin. Nutr., 2009, vol. 90, no. 3, pp. 570–577. DOI: 10.3945/ajcn.2008.27199
  19. Terry M.B., Howe G., Pogoda J.M., Zhang F.F., Ahlbom A., Choi W., Giles G.G., Little J. [et al.]. An international case-control study of adult diet and brain tumor risk: a histology-specific analysis by food group. Ann. Epidemiol., 2009, vol. 19, no. 3, pp. 161–171. DOI: 10.1016/j.annepidem.2008.12.010
  20. Pogoda J.M., Preston-Martin S., Howe G., Lubin F., Mueller B.A., Holly E.A., Filippini G., Peris-Bonet R. [et al.]. An international case-control study of maternal diet during pregnancy and childhood brain tumor risk: a histology-specific analysis by food group. Ann. Epidemiol., 2009, vol. 19, no. 3, pp. 148–160. DOI: 10.1016/j.annepidem.2008.12.011
  21. Wesseling C., Pukkala E., Neuvonen K., Kauppinen T., Boffetta P., Partanen T. Cancer of the brain and nervous system and occupational exposures in Finnish women. J. Occup. Environ. Med., 2002, vol. 44, no. 7, pp. 663–668.
  22. Cocco P., Dosemeci M., Heineman E.F. Brain cancer and occupational exposure to lead. J. Occup. Environ. Med., 1998, vol. 40, no. 11, pp. 937–942. DOI: 10.1097/00043764-199811000-00001
  23. Fallahi P., Elia G., Foddis R., Cristaudo A., Antonelli A. High risk of brain tumors in military personnel: a case control study. Clin. Ter., 2017, vol. 168, no. 6, pp. e376–e379. DOI: 10.7417/T.2017.2037
  24. Piel C., Pouchieu C., Tual S., Migault L., Lemarchand C., Carles C., Boulanger M., Gruber A. [et al.]. Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN. Int. J. Cancer, 2017, vol. 141, no. 9, pp. 1771–1782. DOI: 10.1002/ijc.30879
  25. Vienne-Jumeau A., Tafani C., Ricard D.Environmental risk factors of primary brain tumors: A review. Rev. Neurol. (Paris), 2019, vol. 175, no. 10, pp. 664–678. DOI: 10.1016/j.neurol.2019.08.004
  26. McKean-Cowdin R., Barnholtz-Sloan J., Inskip P.D., Ruder A.M., Butler M., Rajaraman P., Razavi P., Patoka J. [et al.]. Associations between polymorphisms in DNA repair genes and glioblastoma. Cancer. Epidemiol. Biomarkers. Prev., 2009, vol. 18, no. 4, pp. 1118–1126. DOI: 10.1158/1055-9965.EPI-08-1078
  27. Brenner A.V., Linet M.S., Fine H.A., Shapiro W.R., Selker R.G., Black P.M., Inskip P.D. History of allergies and autoimmune diseases and risk of brain tumors in adults. Int. J. Cancer, 2002, vol. 99, no. 22, pp. 252–259. DOI: 10.1002/ijc.10320
  28. Wiemels J.L., Wiencke J.K., Kelsey K.T., Moghadassi M., Rice T., Urayama K.Y., Miike R., Wrensch M. Allergy-related polymorphisms influence glioma status and serum IgE levels. Cancer. Epidemiol. Biomarkers. Prev., 2007, vol. 16, pp. 1229–1235. DOI: 10.1158/1055-9965.EPI-07-0041
  29. Rollison D.E., Helzlsouer K.J., Alberg A.J., Hoffman S., Hou J., Daniel R., Shah K.V., Major E.O. Serum antibodies to JC virus, BK virus, simian virus 40, and the risk of incident adult astrocytic brain tumors. Cancer. Epidemiol. Biomarkers. Prev., 2003, vol. 12, pp. 460–463.
  30. Ding D., Zhao A., Sun Z., Zuo L., Wu A., Sun J.Is the presence of HCMV components in CNS tumors a glioma-specific phenomenon? Virol. J., 2019, vol. 16, pp. 96. DOI: 10.1186/s12985-019-1198-5
  31. Cobbs C.S., Harkins L., Samanta M., Gillespie G.Y., Bharara S., King P.H., Nabors L.B., Cobbs C.G,. Britt W.J. Human cytomegalovirus infection and expression in human malignant glioma. Cancer. Res., 2002, vol. 62, no. 12, pp. 3347–3350.
  32. Stangherlin L.M., Castro F.L., Medeiros R.S., Guerra J.M., Kimura L.M., Shirata N.K., Nonogaki S., Dos Santos C.J., Carlan Silva M.C. Human Cytomegalovirus DNA Quantification and Gene Expression in Gliomas of Different Grades. PLoS One, 2016, vol. 11, pp. e0159604. DOI: 10.1371/journal.pone.0159604

You are here