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.

  • Article
  • Published:

Long-term air pollution exposure and malignant intracranial tumours of the central nervous system: a pooled analysis of six European cohorts

British Journal of Cancer volume 129, pages 656–664 (2023)Cite this article

Subjects

Abstract

Background

Risk factors for malignant tumours of the central nervous system (CNS) are largely unknown.

Methods

We pooled six European cohorts (N = 302,493) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) and malignant intracranial CNS tumours defined according to the International Classification of Diseases ICD-9/ICD-10 codes 192.1/C70.0, 191.0–191.9/C71.0–C71.9, 192.0/C72.2–C72.5. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level.

Results

During 5,497,514 person-years of follow-up (average 18.2 years), we observed 623 malignant CNS tumours. The results of the fully adjusted linear analyses showed a hazard ratio (95% confidence interval) of 1.07 (0.95, 1.21) per 10 μg/m³ NO2, 1.17 (0.96, 1.41) per 5 μg/m³ PM2.5, 1.10 (0.97, 1.25) per 0.5 10−5m−1 BC, and 0.99 (0.84, 1.17) per 10 μg/m³ O3.

Conclusions

We observed indications of an association between exposure to NO2, PM2.5, and BC and tumours of the CNS. The PM elements were not consistently associated with CNS tumour incidence.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Natural spline functions (3 df) of air pollutants and malignant CNS tumour incidence.
Fig. 2: PM2.5 elemental components and malignant CNS tumour incidence (N = 302,493).
Fig. 3: Effect modification by smoking, BMI, and sex on the relation between NO2, PM2.5, BC, and O3 and CNS tumour incidence (N = 302,493).

Similar content being viewed by others

Data availability

The exposure maps are available on request from Dr Kees de Hoogh (c.dehoogh@swisstph.ch). The cohort data is not available for sharing due to strict national data protection regulations and the General Data Protection Regulation of the European Union. The ELAPSE study protocol is available at http://www.elapseproject.eu/. A detailed statistical analysis plan is available on reasonable request from the corresponding author (ullah@cancer.dk).

References

  1. Patel AP, Fisher JL, Nichols E, Abd-Allah F, Abdela J, Abraha HN, et al. Global, regional, and national burden of brain and other CNS cancer, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:376–93.

    Article  Google Scholar 

  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  3. Barnholtz-Sloan JS, Ostrom QT, Cote D. Epidemiology of brain tumors. Neurol Clin. 2018;36:395–419.

    Article  PubMed  Google Scholar 

  4. Hemminki K, Tretli S, Olsen JH, Tryggvadottir L, Pukkala E, Sundquist J, et al. Familial risks in nervous system tumours: joint Nordic study. Br J Cancer. 2010;102:1786–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, et al. The epidemiology of glioma in adults: a "state of the science" review. Neuro Oncol. 2014;16:896–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Navas-Acién A, Pollán M, Gustavsson P, Plato N. Occupation, exposure to chemicals and risk of gliomas and meningiomas in Sweden. Am J Ind Med. 2002;42:214–27.

    Article  PubMed  Google Scholar 

  7. Baldi I, De Graaf L, Bouvier G, Gruber A, Loiseau H, Meryet-Figuiere M, et al. Occupational exposure to pesticides and central nervous system tumors: results from the CERENAT case-control study. Cancer Causes Control. 2021;32:773–82.

    Article  PubMed  Google Scholar 

  8. Röösli M, Lagorio S, Schoemaker MJ, Schüz J, Feychting M. Brain and salivary gland tumors and mobile phone use: evaluating the evidence from various epidemiological study designs. Annu Rev Public Health. 2019;40:221–38.

    Article  PubMed  Google Scholar 

  9. Sergentanis TN, Tsivgoulis G, Perlepe C, Ntanasis-Stathopoulos I, Tzanninis IG, Sergentanis IN, et al. Obesity and risk for brain/cns tumors, gliomas and meningiomas: a meta-analysis. PLoS ONE. 2015;10:e0136974.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Benson VS, Kirichek O, Beral V, Green J. Menopausal hormone therapy and central nervous system tumor risk: large UK prospective study and meta-analysis. Int J Cancer. 2015;136:2369–77.

    Article  CAS  PubMed  Google Scholar 

  11. Cowppli-Bony A, Bouvier G, Rué M, Loiseau H, Vital A, Lebailly P, et al. Brain tumors and hormonal factors: review of the epidemiological literature. Cancer Causes Control. 2011;22:697–714.

    Article  PubMed  Google Scholar 

  12. IARC. IARC monographs on the evaluation of carcinogenic risks to humans. vol. 109. Outdoor air pollution. Lyon: IARC; 2016.

  13. Poulsen AH, Hvidtfeldt UA, Sørensen M, Puett R, Ketzel M, Brandt J, et al. Intracranial tumors of the central nervous system and air pollution—a nationwide case-control study from Denmark. Environ Health. 2020;19:81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Andersen ZJ, Pedersen M, Weinmayr G, Stafoggia M, Galassi C, Jørgensen JT, et al. Long-term exposure to ambient air pollution and incidence of brain tumor: the European Study of Cohorts for Air Pollution Effects (ESCAPE). Neuro Oncol. 2018;20:420–32.

    Article  PubMed  Google Scholar 

  15. Jørgensen JT, Johansen MS, Ravnskjær L, Andersen KK, Bräuner EV, Loft S, et al. Long-term exposure to ambient air pollution and incidence of brain tumours: The Danish Nurse Cohort. Neurotoxicology. 2016;55:122–30.

    Article  PubMed  Google Scholar 

  16. Lagergren M, Fratiglioni L, Hallberg IR, Berglund J, Elmståhl S, Hagberg B, et al. A longitudinal study integrating population, care and social services data. The Swedish National study on Aging and Care (SNAC). Aging Clin Exp Res. 2004;16:158–68.

    Article  PubMed  Google Scholar 

  17. Magnusson PK, Almqvist C, Rahman I, Ganna A, Viktorin A, Walum H, et al. The Swedish Twin Registry: establishment of a biobank and other recent developments. Twin Res Hum Genet. 2013;16:317–29.

    Article  PubMed  Google Scholar 

  18. Wändell PE, Wajngot A, de Faire U, Hellénius ML. Increased prevalence of diabetes among immigrants from non-European countries in 60-year-old men and women in Sweden. Diabetes Metab. 2007;33:30–6.

    Article  PubMed  Google Scholar 

  19. Eriksson AK, Ekbom A, Granath F, Hilding A, Efendic S, Ostenson CG. Psychological distress and risk of pre-diabetes and Type 2 diabetes in a prospective study of Swedish middle-aged men and women. Diabet Med. 2008;25:834–42.

    Article  PubMed  Google Scholar 

  20. Tjønneland A, Olsen A, Boll K, Stripp C, Christensen J, Engholm G, et al. Study design, exposure variables, and socioeconomic determinants of participation in Diet, Cancer and Health: a population-based prospective cohort study of 57,053 men and women in Denmark. Scand J Public Health. 2007;35:432–41.

    Article  PubMed  Google Scholar 

  21. Hundrup YA, Simonsen MK, Jørgensen T, Obel EB. Cohort profile: the Danish nurse cohort. Int J Epidemiol. 2012;41:1241–7.

    Article  PubMed  Google Scholar 

  22. Beulens JW, Monninkhof EM, Verschuren WM, van der Schouw YT, Smit J, Ocke MC, et al. Cohort profile: the EPIC-NL study. Int J Epidemiol. 2010;39:1170–8.

    Article  PubMed  Google Scholar 

  23. Clavel-Chapelon F. Cohort profile: The French E3N Cohort Study. Int J Epidemiol. 2015;44:801–9.

    Article  PubMed  Google Scholar 

  24. Ulmer H, Kelleher CC, Fitz-Simon N, Diem G, Concin H. Secular trends in cardiovascular risk factors: an age-period cohort analysis of 698,954 health examinations in 181,350 Austrian men and women. J Intern Med. 2007;261:566–76.

    Article  CAS  PubMed  Google Scholar 

  25. Hvidtfeldt UA, Severi G, Andersen ZJ, Atkinson R, Bauwelinck M, Bellander T, et al. Long-term low-level ambient air pollution exposure and risk of lung cancer—A pooled analysis of 7 European cohorts. Environ Int. 2021;146:106249.

    Article  CAS  PubMed  Google Scholar 

  26. de Hoogh K, Chen J, Gulliver J, Hoffmann B, Hertel O, Ketzel M, et al. Spatial PM(2.5), NO(2), O(3) and BC models for Western Europe—Evaluation of spatiotemporal stability. Environ Int. 2018;120:81–92.

    Article  PubMed  Google Scholar 

  27. Chen J, de Hoogh K, Gulliver J, Hoffmann B, Hertel O, Ketzel M, et al. Development of Europe-wide models for particle elemental composition using supervised linear regression and random forest. Environ Sci Technol. 2020;54:15698–709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Eeftens M, Beelen R, de Hoogh K, Bellander T, Cesaroni G, Cirach M, et al. Development of Land Use Regression models for PM(2.5), PM(2.5) absorbance, PM(10) and PM(coarse) in 20 European study areas; results of the ESCAPE project. Environ Sci Technol. 2012;46:11195–205.

    Article  CAS  PubMed  Google Scholar 

  29. Brandt J, Silver JD, Frohn LM, Geels C, Gross A, Hansen AB, et al. An integrated model study for Europe and North America using the Danish Eulerian Hemispheric Model with focus on intercontinental transport of air pollution. Atmos Environ. 2012;53:156–76.

    Article  CAS  Google Scholar 

  30. Straif K, Cohen A, Samet J. Air pollution and cancer. Lyon: World Health Organization; 2013.

  31. Chen ST, Lin CC, Liu YS, Lin C, Hung PT, Jao CW, et al. Airborne particulate collected from central Taiwan induces DNA strand breaks, Poly(ADP-ribose) polymerase-1 activation, and estrogen-disrupting activity in human breast carcinoma cell lines. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2013;48:173–81.

    Article  CAS  PubMed  Google Scholar 

  32. Xie W, You J, Zhi C, Li L. The toxicity of ambient fine particulate matter (PM2.5) to vascular endothelial cells. J Appl Toxicol. 2021;41:713–23.

    Article  CAS  PubMed  Google Scholar 

  33. Calderón-Garcidueñas L, Azzarelli B, Acuna H, Garcia R, Gambling TM, Osnaya N, et al. Air pollution and brain damage. Toxicol Pathol. 2002;30:373–89.

    Article  PubMed  Google Scholar 

  34. Genc S, Zadeoglulari Z, Fuss SH, Genc K. The adverse effects of air pollution on the nervous system. J Toxicol. 2012;2012:782462.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Costa LG, Cole TB, Coburn J, Chang YC, Dao K, Roqué PJ. Neurotoxicity of traffic-related air pollution. Neurotoxicology. 2017;59:133–9.

    Article  CAS  PubMed  Google Scholar 

  36. Gjerstorff ML. The Danish Cancer Registry. Scand J Public Health. 2011;39:42–5.

    Article  PubMed  Google Scholar 

  37. Barlow L, Westergren K, Holmberg L, Talbäck M. The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol. 2009;48:27–33.

    Article  PubMed  Google Scholar 

  38. Hackl M, Waldhoer T. Estimation of completeness of case ascertainment of Austrian cancer incidence data using the flow method. Eur J Public Health. 2013;23:889–93.

    Article  PubMed  Google Scholar 

  39. van der Willik KD, Ruiter R, van Rooij FJA, Verkroost-van Heemst J, Hogewoning SJ, Timmermans K, et al. Ascertainment of cancer in longitudinal research: The concordance between the Rotterdam Study and the Netherlands Cancer Registry. Int J Cancer. 2020;147:633–40.

    Article  PubMed  Google Scholar 

  40. Evangelopoulos D, Katsouyanni K, Keogh RH, Samoli E, Schwartz J, Barratt B, et al. PM2.5 and NO2 exposure errors using proxy measures, including derived personal exposure from outdoor sources: a systematic review and meta-analysis. Environ Int. 2020;137:105500.

    Article  CAS  PubMed  Google Scholar 

  41. Beelen R, Hoek G, Fischer P, Brandt PAVD, Brunekreef B. Estimated long-term outdoor air pollution concentrations in a cohort study. Atmos Environ. 2007;41:1343–58.

    Article  CAS  Google Scholar 

  42. Cesaroni G, Porta D, Badaloni C, Stafoggia M, Eeftens M, Meliefste K, et al. Nitrogen dioxide levels estimated from land use regression models several years apart and association with mortality in a large cohort study. Environ Health. 2012;11:48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gulliver J, Morris C, Lee K, Vienneau D, Briggs D, Hansell A. Land use regression modeling to estimate historic (1962-1991) concentrations of black smoke and sulfur dioxide for Great Britain. Environ Sci Technol. 2011;45:3526–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chen J, de Hoogh K, Gulliver J, Hoffmann B, Hertel O, Ketzel M, et al. A comparison of linear regression, regularization, and machine learning algorithms to develop Europe-wide spatial models of fine particles and nitrogen dioxide. Environ Int. 2019;130:104934.

    Article  CAS  PubMed  Google Scholar 

  45. Brunekreef B, Strak M, Chen J, Andersen ZJ, Atkinson R, Bauwelinck M, et al. Mortality and morbidity effects of long-term exposure to low-level PM(2.5), BC, NO(2), and O(3): an analysis of European Cohorts in the ELAPSE project. Res Rep Health Eff Inst. 2021;208:1–127.

Download references

Acknowledgements

We thank Marjan Tewis for the data management tasks in creating the pooled cohort database and the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution to the ELAPSE Study.

Funding

The research described in this article was conducted under contract to the Health Effects Institute (HEI), an organisation jointly funded by the United States Environmental Protection Agency (EPA) (Assistance Award No. R-82811201) and certain motor vehicle and engine manufacturers. The contents of this article do not necessarily reflect the views of HEI, or its sponsors, nor do they necessarily reflect the views and policies of the EPA or motor vehicle and engine manufacturers.

Author information

Authors and Affiliations

  1. Danish Cancer Society Research Center, Copenhagen, Denmark

    Ulla Arthur Hvidtfeldt, Anne Tjønneland & Ole Raaschou-Nielsen

  2. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands

    Jie Chen, Maciej Strak, Bert Brunekreef & Gerard Hoek

  3. Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Sophia Rodopoulou, Klea Katsouyanni & Evangelia Samoli

  4. National Institute for Public Health and the Environment, Bilthoven, The Netherlands

    Maciej Strak

  5. Swiss Tropical and Public Health Institute, Basel, Switzerland

    Kees de Hoogh

  6. University of Basel, Basel, Switzerland

    Kees de Hoogh

  7. Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    Zorana J. Andersen, Rina So, Anne Tjønneland & Jiawei Zhang

  8. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Tom Bellander, Karin Leander, Göran Pershagen & Massimo Stafoggia

  9. Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden

    Tom Bellander & Göran Pershagen

  10. Department of Environmental Science, Aarhus University, Roskilde, Denmark

    Jørgen Brandt, Matthias Ketzel & Ole Raaschou-Nielsen

  11. iClimate—interdisciplinary Centre for Climate Change, Aarhus University, Roskilde, Denmark

    Jørgen Brandt

  12. MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    Daniela Fecht, John Gulliver & Klea Katsouyanni

  13. Department of Epidemiology, Lazio Region Health Service/ASL Roma 1, Rome, Italy

    Francesco Forastiere & Massimo Stafoggia

  14. Environmental Research Group, School of Public Health, Faculty of Medicine, Imperial College, London, London, UK

    Francesco Forastiere

  15. Centre for Environmental Health and Sustainability & School of Geography, Geology and the Environment, University of Leicester, Leicester, UK

    John Gulliver

  16. Departments of Ecoscience, Aarhus University, Roskilde, Denmark

    Ole Hertel

  17. Institute for Occupational, Social and Environmental Medicine, Centre for Health and Society, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    Barbara Hoffmann

  18. Global Centre for Clean Air Research (GCARE), University of Surrey, Guildford, GU2 7XH, UK

    Matthias Ketzel

  19. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Patrik K. E. Magnusson

  20. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany

    Gabriele Nagel & Gudrun Weinmayr

  21. Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden

    Debora Rizzuto

  22. Stockholm Gerontology Research Center, Stockholm, Sweden

    Debora Rizzuto

  23. Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany

    Kathrin Wolf

  24. Agency for Preventive and Social Medicine (aks), Bregenz, Austria

    Emanuel Zitt

  25. Department of Internal Medicine 3, LKH Feldkirch, Feldkirch, Austria

    Emanuel Zitt

Authors
  1. Ulla Arthur Hvidtfeldt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophia Rodopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maciej Strak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kees de Hoogh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zorana J. Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tom Bellander
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jørgen Brandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daniela Fecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Francesco Forastiere
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. John Gulliver
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ole Hertel
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Barbara Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Klea Katsouyanni
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Matthias Ketzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Karin Leander
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Patrik K. E. Magnusson
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Gabriele Nagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Göran Pershagen
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Debora Rizzuto
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Evangelia Samoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Rina So
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Massimo Stafoggia
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Anne Tjønneland
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Gudrun Weinmayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Kathrin Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Jiawei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Emanuel Zitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Bert Brunekreef
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Gerard Hoek
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Ole Raaschou-Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GH, ORN and UAH: study conceptualisation and design; GH and BB: principal investigators of the ELAPSE project; UAH: statistical analysis and manuscript writing; GH, ORN and BB: supervision, manuscript review and editing; GH, BB, JC and MS: ELAPSE project coordination, preparing pooled data for analyses, and providing support with the access to pooled cohort data; SR, ES and KK: contribution of statistical analyses strategy and scripts for the statistical analyses; KdH, JC and GH: exposure assessment; JB: exposure data. All authors contributed to the interpretation of the results. All authors read and revised the manuscript for the important intellectual content and approved the final draft of the manuscript.

Corresponding author

Correspondence to Ulla Arthur Hvidtfeldt.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study involved no contact with members of the study population and the published results does not allow identification of individuals. The analyses were undertaken in a secure IT environment where no individual level data can be retrieved. All included cohort studies were approved by the medical ethics committees in their respective countries.

Consent for publication

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hvidtfeldt, U.A., Chen, J., Rodopoulou, S. et al. Long-term air pollution exposure and malignant intracranial tumours of the central nervous system: a pooled analysis of six European cohorts. Br J Cancer 129, 656–664 (2023). https://doi.org/10.1038/s41416-023-02348-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-023-02348-1

Search

Advanced search

Quick links