Angela Zumel-Marne et al. Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study. J Neurooncol. 2020 Apr;147(2):427-440. doi: 10.1007/s11060-020-03437-4. Epub 2020 Mar 3. DOI: 10.1007/s11060-020-03437-4.
Introduction: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24).
Methods: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location.
Results: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays.
Conclusions: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.
"The overall objective of the current project was to assess the potential carcinogenic effects of childhood and adolescent exposure to radio frequency (RF) and extremely low frequency (ELF) from mobile telephones on tumours of the central nervous system.
- To conduct a multinational epidemiological case-control study of brain tumours diagnosed in young people in relation to electro-magnetic fields (EMF) exposure from mobile telephones and other sources of RF in eight countries under the current grant, and, subject to funds being secured separately, in a number of non-European countries;
- To develop and validate improved indices of RF and extremely low frequency (ELF) exposure, and assess related uncertainties, for all subjects in the study;
- To analyse the relation between risk of brain tumours and exposures to RF and ELF from mobile phones and other relevant and important sources of exposure in young people’s general environment.
The MOBI-KIDS project was conducted in 14 countries (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, New Zealand, Spain, The Netherlands) between 2010 and 2015. It used a case-control study design, recruiting 898 eligible cases aged 10 to 24 years old and 1 912 controls matched to the cases on reference date, study region and age.
Each participant completed a face-to-face interview that included information on socio-demographic factors; complete residential history; exposure to farm and domestic animals; mobile phone use; use of other wireless communication devices including cordless phones and Wi-Fi; exposure to other environmental and occupational sources of EMF; occupational history of the subject and his/her parents during the peri-conception, pregnancy and peri-natal period; occupational exposures to ionising radiation and chemicals; medical radiation exposure; medical history of the subject and mother and water and disinfection by-products exposure (the later only in 6 countries). Interviewers completed a questionnaire regarding responsiveness of the interviewee and quality of recall.
Among regular users of mobile phones, the mean time since start of mobile phone use was 6.2 years for controls, with high differences by age group: 3.2 years for the younger age group (10-14) and 9.2 years for the older age group (20-24), respectively; in the latter group, 37% of controls reported using a phone for 10 years or more. Average number of calls per month was 43 for cases and 49 for controls – with 5% of cases and 4% of controls making more than 10 calls per day on average –, and average hours per month talking on the mobile phone were 2.1 and 2.6 respectively – 4% of case and 3% of controls used the phone for calling more than 1 hour per month on average. In both indicators of mobile phone use, we observed an increasing trend in number of calls and average call time with age.
Analyses of the association between mobile phone use and brain tumour risk, as well as between estimated RF and ELF exposure at the location of the tumour and risk of brain tumour have been conducted and a publication is in preparation. Results however cannot be made public until publication in a peer-reviewed scientific journal.
Research on the adverse effects of mobile phone radiation has focused on the radiofrequency (RF) emissions from cell phones and cordless phones and has ignored the effects of the extremely low frequency fields (ELF) produced by the phones. Yet ELF was labelled "possibly carcinogenic to humans" by the WHO International Agency for Research on Cancer a decade earlier than RF.
The paper below indicates that the MOBI-Kids research team is studying the effects of exposure to ELF as well as RF on children's cancer risk from mobile and cordless phone use.
Calderón C, Ichikawa H, Taki M, Wake K, Addison D, Mee T, Maslanyj M, Kromhout H, Lee AK, Sim MR, Wiart J, Cardis E. ELF exposure from mobile and cordless phones for the epidemiological MOBI-Kids study. Environ Int. 2017 Jan 23. pii: S0160-4120(17)30047-8. doi: 10.1016/j.envint.2017.01.005. [Epub ahead of print]
This paper describes measurements and computational modelling carried out in the MOBI-Kids case-control study to assess the extremely low frequency (ELF) exposure of the brain from use of mobile and cordless phones. Four different communication systems were investigated: Global System for Mobile (GSM), Universal Mobile Telecommunications System (UMTS), Digital Enhanced Cordless Telecommunications (DECT) and Wi-Fi Voice over Internet Protocol (VoIP). The magnetic fields produced by the phones during transmission were measured under controlled laboratory conditions, and an equivalent loop was fitted to the data to produce three-dimensional extrapolations of the field. Computational modelling was then used to calculate the induced current density and electric field strength in the brain resulting from exposure to these magnetic fields. Human voxel phantoms of four different ages were used: 8, 11, 14 and adult. The results indicate that the current densities induced in the brain during DECT calls are likely to be an order of magnitude lower than those generated during GSM calls but over twice that during UMTS calls. The average current density during Wi-Fi VoIP calls was found to be lower than for UMTS by 30%, but the variability across the samples investigated was high. Spectral contributions were important to consider in relation to current density, particularly for DECT phones. This study suggests that the spatial distribution of the ELF induced current densities in brain tissues is determined by the physical characteristics of the phone (in particular battery position) while the amplitude is mainly dependent on communication system, thus providing a feasible basis for assessing ELF exposure in the epidemiological study. The number of phantoms was not large enough to provide definitive evidence of an increase of induced current density with age, but the data that are available suggest that, if present, the effect is likely to be very small.
According to the European Commission, the EU-funded project "Risk of brain cancer from exposure to radiofrequency fields in childhood and adolescence" (MOBI-Kids) was "closed" on Feb 29, 2016. The study will make an important contribution to assessing the association, if any, between electromagnetic field exposure due to use of mobile communication devices and the development of brain cancer in youth.
From December, 2010 through February, 2015, about 800 cases and 1,600 controls were interviewed for this study.
This is a difficult case-control study to undertake as it involves 14 nations and about 60 senior investigators. The original goal was to recruit 2,000 cases. The authors revised the original goal to 1,000 cases because recruitment of cases has been much more difficult than anticipated. As of June, 2014, only 686 cases were recruited, and 566 were interviewed. Only six more months remain for participant recruitment. Thus, even the reduced recruitment goal may be difficult to achieve.
I am concerned that the MOBI-Kids study will fail to have adequate statistical power to detect the association between EMF exposure and brain tumor risk. The CEFALO study of brain tumor risk in children was seriously under-powered with 352 cases (Aydin et al., 2011; http://bit.ly/1pW4ulA). The four nation CEFALO study found a 36% increased relative risk of brain tumors with any mobile phone use, but this was not statistically significant due to the small sample size (OR = 1.36; 95% CI = 0.92 to 2.02) so the authors dismissed this overall finding. (See my supplementary comments below because CEFALO found some statistically significant evidence for increased brain tumor risk which the study authors also dismissed.)
Sadetzki S, Langer CE, Bruchim R, Kundi M, Merletti F, Vermeulen R, Kromhout H, Lee A-K, Maslanyj M, Sim MR, Taki M, Wiart J, Armstrong B, Milne E, Benke G, Schattner R, Hutter H-P, Woehrer A, Krewski D, Mohipp C, Momoli F, Ritvo P, Spinelli J, Lacour B, Delmas D, Remen T, Radon K, Weinmann T, Klostermann S, Heinrich S, Petridou E, Bouka E, Panagopoulou P, Dikshit R, Nagrani R, Even-Nir H, Chetrit A, Maule M, Migliore E, Filippini G, Miligi L, Mattioli S, Yamaguchi N, Kojimahara N, Ha M, Choi K-H, Mannetje A’, Eng A, Woodward A, Carretero G, Alguacil J, Aragones N, Suare-Varela MM, Goedhart G, Schouten-van Meeteren AAYN, Reedijk AAMJ and Cardis E (2014) The MOBI-Kids study protocol: challenges in assessing childhood and adolescent exposure to electromagnetic fields from wireless telecommunication technologies and possible association with brain tumor risk. Front. Public Health 2:124. Sep 23, 2014. doi: 10.3389/fpubh.2014.00124.
The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries.
The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges.
This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including:
(1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls;
(2) investigating a young study population spanning a relatively wide age range;
(3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements;
(4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies.
Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.
Open Access: http://bit.ly/1pVKGyS
The original expected number of cases in the target age range was of the order of 2,000. With the implementation of the study, however, it became apparent that the number of eligible cases is, in fact, much lower, in large part due to an underestimation of the number of midline tumors in the study population and, to a lesser extent, the failure of busy medical staff to notify eligible patients in some centers. In most centers, it is difficult to know exactly how many cases are ineligible as doctors/hospital staff will generally not inform study staff of ineligible cases. However, centers with access to detailed, reliable registry information or hospital records have excluded from one-third to more than one-half of cases due to an ineligible (midline) diagnosis. Table 1 indicates the revised expected number of eligible cases per year; the revised expected total number of cases to be included in MOBI-Kids is around 1,000, based on each center’s length of time in the field and other factors such as number of participating hospitals and accessibility to eligible cases. Fortunately, the MOBI-Kids study still has sufficient statistical power despite the reduced number of cases (see Study Power below).
Daniel Krewski has conducted contract work for the federal government of Canada (specifically, the Public Health Agency of Canada and Industry Canada) involving systematic review and summary of scientific information on potential health effects of radiofrequency fields. Malcolm R. Sim – wife had shares of Cell Phone Company. Masao Taki’s department received a grant to support numerical modeling work under a university–industry partnership. Joe Wiart works at Whist Laboratory funded by Orange. None of this funding was used to support the research described in this paper. The other authors declare that they have no conflict of interest.
Fourteen participating nations: Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Netherlands, New Zealand, and Spain.
Diagnostic period: May, 2010 through December, 2014.
Participation rates (to date) (http://bit.ly/1CYvnO7):
78-83% of cases and 60-69% of controls.
Main characteristics of 566 cases and 1074 controls (thru June, 2014) (http://bit.ly/1BXvbfr):
Sex: 55% male, 45% female.
Years of age: 40% 10-14; 35% 15-19; 24% 20-24.
Most of the cases came from six countries: Spain (145), Italy (106), Germany (71), Israel (65) , France (63), or Greece (42). The eight other countries have so far only contributed 2 to 23 cases each.
"It's a very peculiar paper and even more peculiar that it's published in a journal sponsored by the National Cancer Institute," Joel Moskowitz, director of the Center for Family and Community Health at the University of California-Berkeley, told Life's Little Mysteries. A red flag, he said, is that the research was funded in part by the cellphone industry, and some of the investigators also do other industry-funded research.
In Moskowitz's opinion, the conclusions drawn by study leader Martin Röösli, an environmental epidemiologist at the Swiss Tropical and Public Health Institute, and his colleagues were biased to downplay concerns about cellphone use among children and adolescents.
In a response sent to the media, Moskowitz pointed out what he considers several flaws in Röösli's logic, starting with how little cellphone use (one call per week) counted as "regular." This parameter flooded the pool of truly regular cellphone users with almost-non-users, he said, skewing the results. "Such a loose definition of regular use would be expected to reduce the association between cellphone use and tumor risk," Moskowitz wrote. [FAQ: Cellphone Radiation and Brain Cancer]
When a subset of the data corresponding only to heavy cellphone users is analyzed, he pointed out, the results become much more striking. From the journal's paper itself: "[There] was a highly significant association between the time since first subscription and brain tumor risk. Children who used cellphones for at least 2.8 years were more than twice as likely to have a brain tumor than those who never regularly used cellphones." The authors went on to state: "As compared to never regular users, those who used cellphones for 4 or more years based on phone company records were 3.7 to 4.0 times more likely to have brain tumors, and those who made 2,638 or more calls were 2.9 to 4.8 times more likely to have brain tumors."
Brain tumors are the second most common cancer in young people under 20 years of age. The incidence has been increasing recently. (1)
CEFALO, a small, four-country, case-control study of brain tumors in children, found in a subgroup for whom phone company data were available that brain tumor risk was related to the number of years the children had a mobile phone subscription. The study found elevated risks (though not statistically significant) for children who used mobile phones in three of the four countries (Denmark, Sweden and Switzerland), but not in Norway or overall. The study had 352 young people 7-19 years of age with brain tumors and 646 healthy young people. (2)
In a case-control study, persons who have developed a disease are identified and their past exposure to potential etiological factors is compared to persons who do not have the disease. (1)
MOBI-KIDS is a large, 16-country, case-control study that will evaluate the association between mobile phone and other communication technology use, other environmental exposures, and the risk of brain tumors in young people. MOBI-KIDS will include about 2.000 young people 10-24 years of age with brain tumors and about 4.000 healthy young people. Results will be available in 2015/2016. (3)
Just like the INTERPHONE study which examined brain tumors in adults, Canada is participating in the MOBI-KIDS study, but the U.S. is not. (4)
Why has the U.S. failed to participate in these international studies? Why does the U.S. fund so little research on the health risks of exposure to electromagnetic radiation?
(1) Frequently Asked Questions | MOBI-KIDS. http://www.mbkds.com/frequently-asked-questions-0
(2) Aydin D., et al. Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.J Natl Cancer Inst. 2011 Aug 17;103(16):1264-76. doi: 10.1093/jnci/djr244. Epub 2011 Jul 27. http://jnci.oxfordjournals.org/content/103/16/1264.long
(3) Welcome | MOBI-KIDS: Study on Communication Technology, Environment, and Brain Tumours in Young People. http://www.mbkds.com/home
(4) Partners | MOBI-KIDS. http://www.mbkds.com/list-of-partners
May 12, 2015
"Another paper published by Prof. Sadetzki and Prof. Cardis in 2011 entitled: "Indications of possible brain-tumor risk in mobile-phone studies: should we be concerned?" (Occup Environ Med. 2011 Mar;68(3):169-71), discusses the main issues in the interpretation of the findings reported in published studies of brain tumors in relation to mobile-phone use, particularly the largest of these, Interphone, and their potential public-health implications.
The authors concluded that while more studies are needed to confirm or refute these results, indications of an increased risk in high- and long-term users from Interphone and other studies are of concern.
Since more than 4 billion people, including children, using mobile phones even a small risk at the individual level could eventually result in a considerable number of tumors and become an important public-health issue.
The authors suggested that until definitive scientific answers are available, simple and low-cost measures, such as the use of text messages, hands-free kits and/or the loud-speaker mode of the phone should be used to reduce exposure to the brain from mobile phones."
Assessment of extremely low frequency magnetic field exposure from GSM mobile phones
The study demonstrates that the phones emit magnetic flux densities at 217 Hz and associated harmonics, and could contribute substantially to ELF exposure in the general population. It is therefore not unreasonable to include a measure of this exposure in epidemiological studies assessing the potential risk of EMF exposure and brain tumor, particularly for young people, for whom the time weighted average exposure, over lifetime, may be greater than in adults.
Due to the technological advancements in mobile telecommunications during the study period of interest (2000–2013), it will also be necessary to assess 2.5–3.5 G phones; Enhanced Data rates for GSM Evolution (EDGE), Universal Mobile Telecommunications System (UMTS), High Speed Packet Access (HSPA) and Digital Enhanced Cordless Telecommunications (DECT) phones as well as the 2G phones.
Conflicts of interest: Prof. Masao Taki's department received a grant to support numerical modeling work under a university-industry partnership. Whist Lab is funded by France Telecom. None of this funding was used to support the research described in this paper.