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CEFALO: An international case-control study on brain tumours in children and adolescents

English title CEFALO: An international case-control study on brain tumours in children and adolescents
Applicant Röösli Martin
Number 122873
Funding scheme ProDoc
Research institution Institut für Sozial- und Präventivmedizin Universität Basel Swiss TPH
Institution of higher education University of Basel - BS
Main discipline Cancer
Start/End 01.02.2009 - 31.01.2012
Approved amount 160'834.03
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All Disciplines (2)

Discipline
Cancer
Other disciplines of Environmental Sciences

Keywords (9)

childhood brain tumour; epidemiology; mobile phone; case-control study; mobile phone; brain tumour; epidemiology; non-ionizing radiation; radiofrequency electromagnetic fields

Lay Summary (English)

Lead
Lay summary

Background: Mobile phone use among adults and children has increased considerably in the past 15 years. This led to concerns in the general public about possible adverse health effects of radiofrequency electromagnetic fields generated by mobile phones. So far, the risk of brain tumors due to mobile phone use has not been addressed in children and adolescents.

Aim: CEFALO is an international case-control study examining the association between mobile phone use and the risk of brain tumors among children and adolescents.

Methods: The study was conducted in Denmark, Sweden, Norway, and Switzerland. All children aged 7 to 19 years and diagnosed with a brain tumor between 2004 and 2008 were eligible for the study. For each patient, two controls of the same age, gender and region of residence were randomly selected from population registries. Exposure data was obtained by personal face-to-face interviews with the study participants and their parents. The frequency and duration of mobile phone use was inquired for various time periods as well as the preferred side of the head. Furthermore, we asked for permission to obtain connection data from mobile phone network operators. The association between mobile phone use and brain tumor risk was evaluated by comparing the duration and intensity of mobile phone use between case patients and controls in conditional logistic regression analyses. Several sensitivity analyses were also calculated.

Results: Overall, 352 patients and 646 controls took part in the study. Participation rates were 83% for cases and 71% for controls. Fifty-five percent of the patients and 51% of controls reported regular mobile phone use (at least one cal per week during at least 6 months). Brain tumor risk was not significantly associated with regular use of mobile phones (Odds ratio [OR]=1.36, 95% Confidence interval [CI]=0.92–2.02). Other exposure metrics such as time since first use or cumulative number and duration of calls were also not significantly associated with brain tumors and not consistent exposure-response relationship was observed. The risk of brain tumors in the regions of the brain that receive most radiation was not associated with regular mobile phone use. Tumors did not occur more often on the ipsilateral compared to the contralateral side. Objective operator data were available for a third of the study participants, who reported to be subscribers. In this subset, brain tumor risk was elevated for participants with the longest period since first subscriptions (> 2.8 years; OR=2.15, 95%-CI: 1.07–4.29). Calculations demonstrated that such a risk, if true, would have resulted in the increase of brain tumor incidence by approximately 50% in the last few years. Such an increase was not observed in Swedish children and adolescents.

Discussion: CEFALO is the first study addressing the possible relationship between mobile phone use and brain tumor risk among children and adolescents. The regression analyses revealed several somewhat elevated risk estimates but none was statistically significant. The pattern of the risk results does not suggest a causal relationship. In most of the analyses, no exposure-response relationship could be observed. Further, brain tumor risk was not elevated in brain regions that are most exposed during calls. Also, brain tumor incidence in children and adolescents in Sweden has rather decreased than increased between 2000 and 2008. In summary, the results of CEFALO do not suggest a causal association between mobile phone use and brain tumor risk. However, since the duration and intensity of use was relatively low in our sample we were not able to evaluate brain tumor risk regarding intensive long term mobile phone use. Given the substantial amount of mobile phone use among adolescents today and the methodological limitations of case-control studies in this research area, incidence trends of brain tumors should be carefully monitored in the next years using high quality registry data.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.
Vienneau Danielle, Infanger Denis, Feychting Maria, Schüz Joachim, Schmidt Lisbeth Samsø, Poulsen Aslak Harbo, Tettamanti Giorgio, Klæboe Lars, Kuehni Claudia E, Tynes Tore, Von der Weid Nicolas, Lannering Birgitta, Röösli Martin (2016), A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data., in Cancer epidemiology, 40, 52-9.
Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility.
Adel Fahmideh Maral, Lavebratt Catharina, Schüz Joachim, Röösli Martin, Tynes Tore, Grotzer Michael A, Johansen Christoffer, Kuehni Claudia E, Lannering Birgitta, Prochazka Michaela, Schmidt Lisbeth S, Feychting Maria (2016), Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility., in Oncotarget, 1.
Prenatal and Postnatal Medical Conditions and the Risk of Brain Tumors in Children and Adolescents: An International Multicenter Case-Control Study.
Tettamanti Giorgio, Shu Xiaochen, Adel Fahmideh Maral, Schüz Joachim, Röösli Martin, Tynes Tore, Grotzer Michael, Johansen Christoffer, Klaeboe Lars, Kuehni Claudia E, Lannering Birgitta, Schmidt Lisbeth S, Vienneau Danielle, Feychting Maria (2016), Prenatal and Postnatal Medical Conditions and the Risk of Brain Tumors in Children and Adolescents: An International Multicenter Case-Control Study., in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer , 26(1), 110-115.
Atopic conditions and brain tumor risk in children and adolescents--an international case-control study (CEFALO).
Shu X, Prochazka M, Lannering B, Schüz J, Röösli M, Tynes T, Kuehni C E, Andersen T V, Infanger D, Schmidt L S, Poulsen A H, Klaeboe L, Eggen T, Feychting M (2014), Atopic conditions and brain tumor risk in children and adolescents--an international case-control study (CEFALO)., in Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 25(4), 902-8.
CCDC26, CDKN 2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility
Fahmideh Maral Adel, Lavebratt Catharina, Schüz Joachim, Röösli Martin, Röösli Martin, Tynes Tore, Tynes Tore, A.Grotzer Michael, Johansen Christoffer, Johansen Christoffer, E.Kuehni Claudia, Lannering Birgitta, Prochazka Michaela, S.Schmidt Lisbeth, Feychting Maria (2014), CCDC26, CDKN 2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility, in Carcinogenesis, 36(8), 876-882.
Use of Mobile Phones and Brain Cancer Risk in Children?
Röösli M., Feychting M., Schüz J. (2014), Use of Mobile Phones and Brain Cancer Risk in Children?, in Hayat M.A. (ed.), Springer, ebook, 293-300.
Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents: an International Case-Control Study (CEFALO).
Andersen T V, Schmidt L S, Poulsen A H, Feychting M, Röösli M, Tynes T, Aydin D, Prochazka M, Lannering B, Klæboe L, Eggen T, Kuehni C E, Schmiegelow K, Schüz J (2013), Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents: an International Case-Control Study (CEFALO)., in British journal of cancer, 108(11), 2346-53.
Brain tumors in children and adolescents and exposure to animals and farm life: a multicenter case-control study (CEFALO).
Christensen Jeppe Schultz, Mortensen Laust Hvas, Röösli Martin, Feychting Maria, Tynes Tore, Andersen Tina Veje, Schmidt Lisbeth Samsø, Poulsen Aslak Harbo, Aydin Denis, Kuehni Claudia E, Prochazka Michaela, Lannering Birgitta, Klaeboe Lars, Eggen Tone, Schüz Joachim (2012), Brain tumors in children and adolescents and exposure to animals and farm life: a multicenter case-control study (CEFALO)., in Cancer causes & control : CCC, 23(9), 1463-73.
Childhood brain tumours and use of mobile phones: comparison of a case–control study with incidence data
Aydin Denis, Feychting Maria, Schüz Joachim, Röösli Martin (2012), Childhood brain tumours and use of mobile phones: comparison of a case–control study with incidence data, in Environmental Health, 11, 35.
Re: Mobile Phone Use and Brain Tumors in Children and Adolescents Response
Aydin D, Feychting M, Schuz J, Roosli M (2012), Re: Mobile Phone Use and Brain Tumors in Children and Adolescents Response, NN, NN.
Re: Mobile Phone Use and Brain Tumors in Children and Adolescents: A Multicenter Case-Control Study Response
Aydin D, Feychting M, Schuz J, Roosli M (2012), Re: Mobile Phone Use and Brain Tumors in Children and Adolescents: A Multicenter Case-Control Study Response, NN, NN.
Impact of random and systematic recall errors and selection bias in case--control studies on mobile phone use and brain tumors in adolescents (CEFALO study).
Aydin Denis, Feychting Maria, Schüz Joachim, Andersen Tina Veje, Poulsen Aslak Harbo, Prochazka Michaela, Klaeboe Lars, Kuehni Claudia E, Tynes Tore, Röösli Martin (2011), Impact of random and systematic recall errors and selection bias in case--control studies on mobile phone use and brain tumors in adolescents (CEFALO study)., in Bioelectromagnetics, 32(5), 396-407.
Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.
Aydin Denis, Feychting Maria, Schüz Joachim, Tynes Tore, Andersen Tina Veje, Schmidt Lisbeth Samsø, Poulsen Aslak Harbo, Johansen Christoffer, Prochazka Michaela, Lannering Birgitta, Klæboe Lars, Eggen Tone, Jenni Daniela, Grotzer Michael, Von der Weid Nicolas, Kuehni Claudia E, Röösli Martin (2011), Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study., in Journal of the National Cancer Institute, 103(16), 1264-76.
Predictors and overestimation of recalled mobile phone use among children and adolescents
Aydin D, Feychting M, Schüz J, Veje Andersen T, Harbo Poulsen A, Prochazka M, Klæboe L, Kuehni CE, Tynes T, Röösli M (2011), Predictors and overestimation of recalled mobile phone use among children and adolescents, in Progress in Biophysics and Molecular Biology, 107(3), 356-361.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
COST short term mission, reference code: COST-STSM-BM0704-05358. Talk given at a conference Environmental risk factors for children 12.10.2009 Basel, Slovenia Röösli Martin;


Communication with the public

Communication Title Media Place Year
Media relations: radio, television Brain cancer in children and mobile phone use Worldwide media coverage after article press release of JNCI Western Switzerland International 2011
Print (books, brochures, leaflets) CEFALO: Internationale Fall-Kontrollstudie zu den Ursachen von Hirntumoren bei Kindern und Jugendlic German-speaking Switzerland 2011
Media relations: radio, television Hirntumore bei Kindern nicht wegen Handystrahlung SF1, Hauptausgabe Tagesschau German-speaking Switzerland 2011

Associated projects

Number Title Start Funding scheme
124951 Domestic radon exposure and risk of childhood cancer 01.06.2009 ProDoc
138190 HERMES: Health Effects Related to Mobile Phone Use in Adolescents 01.01.2012 Project funding (Div. I-III)
113595 Prospektive Kohortenstudie zum Einfluss der nicht ionisierenden Strahlung auf die gesundheitsbezogene Lebensqualität 01.01.2007 NRP 57 Non-Ionising Radiation - Health and Environment

Abstract

Background: It has been hypothesized, that children could be more vulnerable to radio frequency electromagnetic field exposures from mobile telephones than adults, but no epidemiological studies of the relationship have been performed so far. The lack of knowledge causes conflicting recommendations from decision-makers, leading to anxiety and insecurity in the population. WHO and The National Academies (USA) has put a case-control study on childhood brain tumours as high priority on their research agenda on radio frequency electromagnetic fields. In 2006, CEFALO, a multinational case-control study of the association between the use of mobile telephones and the risk of brain tumours among children aged 7-19 years has been set up in Denmark, Norway, Sweden, United Kingdom and Switzerland. The PhD project is embedded in this multi-centre study.Methods: Cases are identified through a combination of data from the cancer registries and information from the wards treating the patients. All incident cases of brain tumour between May 2004 and May 2008 are identified, irrespective of vital status at the date of recruitment. In total, the study is expected to include 500 cases of brain tumours in the participating countries, thereof 100 originating from Switzerland. For each case, two control persons will be randomly selected from the general population, matched on age, sex and geographic regions. Information on the extent of exposure to radio frequency fields from mobile phones and on other known and suspected risk factors for childhood brain tumours is obtained by means of personal interviews conducted by an interviewer trained for this purpose. The interviews take place either at the hospital or at the study participant’s home. Objective information on the frequency and duration of mobile phone use will be obtained from mobile phone operators and from the information stored in the telephone that is in current use. In Switzerland all three mobile phone operators (Swisscom, Orange, Sunrise) agreed to provide data on mobile phone use from consenting study participants. Phone traffic records will be available 6 months back in time. Billing records and duration of subscription can be delivered for the whole period since GSM is used. Gene-environment interactions play a role in the expression of the noxious potency of an exogenous environmental agent (e.g. non-ionizing radiation) and thus may modify the individual cancer risk. For that reason we will investigate genetic polymorphisms of DNA repair genes as well as polymorphisms in genes which are involved in the metabolism of toxins. We will collect DNA in the form of saliva in cases and controls. Ethical approval has been obtained in all countries.PhD project: The field work will end in December 2008. Switzerland is in charge to investigate the association between mobile phone use and brain tumour in the whole dataset. The PhD student will be involved in the data cleaning and data management. Subsequently the PhD student will perform the data analyses with the following aims:Using data from the Swiss study arm: •To calculate incidence of brain tumours in Switzerland for children and adolescents aged 7-19 years (2004-2008). •To describe patient flows and referral practices for young brain tumour patients in the Swiss health systemUsing data from all collaborating European centres: •To evaluate the correlation between self reported use of mobile phones and operator data.•To analyse the association between use of mobile phones and risk for brain tumours in children and adolescents.•To participate in the analysis of gene-environment interactions relating to the risk of brain tumours and mobile phonesThe data will be analyzed using established statistical methods for case-control studies, primarily via logistic regression models adjusted for potential confounding factors. Schedule: The PhD will start in October 2008 and last 3 years.
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