Meta-analyse van leukemie bij kinderen: Activiteitenverslag en publicaties

C. Brabant, G. Honvo, C. Demonceau, E. Tirelli, D. Cataldo, O. Bruyère

We voerden (i) een globale meta-analyse uit op basis van alle dierstudies naar de relatie tussen ELF-MF en de incidentie van kanker en (ii) aparte meta-analyses naar de incidentie van kanker op basis van alle studies die een volledige necropsie van de dieren hebben uitgevoerd na blootstelling aan magnetische velden. Onze voorlopige resultaten, voornamelijk gebaseerd op de globale meta-analyse, geven aan dat blootstelling aan ELF-MF geen significant effect had op de incidentie van kanker bij dieren. Ook was de associatie tussen blootstelling aan ELF-MF en de incidentie van kanker niet significant wanneer alle kankers worden gecombineerd in meta-analyses die zich beperkten tot studies waarin een volledige necropsie van de dieren werd uitgevoerd. In het algemeen suggereren onze voorlopige resultaten dat blootstelling aan ELF-MF geen gevaar lijkt te vormen voor zoogdieren. Deze voorlopige resultaten moeten echter voorzichtig worden geïnterpreteerd omdat er rekening moet worden gehouden met aanvullende analyses.

C. Brabant, G. Honvo, C. Demonceau, E. Tirelli, D. Cataldo, O. Bruyère

Er werden reeds veel in vitro studies en dierproeven uitgevoerd om het carcinogeen potentieel van extreem laagfrequente magnetische velden (ELF-EMF) bij knaagdieren en de impact van ELF-MF op DNA te onderzoeken, maar met tegenstrijdige resultaten. Daarom voeren we hier een systematische review en meta-analyse uit om de wetenschappelijke onderzoeken naar de carcinogene effecten van ELF-MF, uitgevoerd met proefdieren en met de comet assay, samen te vatten.
We hebben Medline, Scopus en Embase gebruikt om alle studies op te sporen naar het carcinogene potentieel van extreem laagfrequente magnetische velden. Onze zoekstrategie leverde 5138 referenties op zonder duplicaten. We hebben Covidence gebruikt om de samenvattingen en de volledige teksten te screenen. 384 abstracts voldeden potentieel aan onze inclusiecriteria. Twee onderzoekers hebben de 384 volledige teksten gelezen om te bepalen welke aan onze inclusiecriteria voldeden. 68 artikelen met volledige gegevens voldeden aan onze inclusiecriteria. Drie artikelen zijn geëlimineerd omdat ze ten minste gedeeltelijk op dezelfde gegevens waren gebaseerd. 65 artikelen zijn opgenomen in de kwalitatieve synthese van ons werk. We voeren momenteel de gegevensextractie uit met behulp van een gestandaardiseerd gegevensextractieformulier. De beoordeling van de methodologische kwaliteit is onafhankelijk van elkaar uitgevoerd door de twee beoordelaars. We gebruiken de SYRCLE’s risk of bias tool om de methodologische kwaliteit van de dierstudies te evalueren.

C. Brabant, G. Honvo, C. Demonceau, E. Tirelli, D. Cataldo, O. Bruyère

We have performed a meta-analysis that supports an increased risk of leukemia in children after exposure to extremely low frequency magnetic fields (ELF-MF) and we have published our work in Reviews on Environmental Health (Brabant et al., 2022, Reviews on Environmental Health, doi: 10.1515/reveh-2021-0112). However, the conditions under which ELF-MF represent a risk factor for leukemia are still unclear. For example, the duration of the magnetic field exposure seems to play a critical role for the development of cancers but this is difficult to demonstrate in human studies. Almost all the studies included in our meta-analysis were case-control studies but variables like the magnetic flux density, the frequency and the duration of the magnetic field exposure cannot be manipulated experimentally in these case-control studies. In vitro and animal studies could be relevant to clarify the role of these variables. Since most cancers are initiated by damage to the genome of the cells, several in vitro studies have been conducted to examine the genotoxic effects of magnetic fields on DNA and chromosomal structure. Furthermore, many animal studies have been performed to determine whether exposure to ELF-MF can increase the risk of developing cancer in mammals. Animal models provide the opportunity to investigate the carcinogenetic potential of ELF-MF experimentally and manipulate variables like the magnetic flux density and duration of magnetic field exposure. Nevertheless, there are many discrepancies in this research field. Therefore, we are performing a systematic review and meta-analysis on the carcinogenic effects of ELF-MF based on studies performed with animals and in vitro to clarify the conditions under which ELF-MF can promote cancer and leukemia development. In this report, we describe our protocol, our search strategy and the methods we have used to select studies. Our protocol describes the methods used in our systematic review and has been published in Prospero in May 2022 (Registration number: CRD42022321862). Medline, Scopus and Embase database searches have been performed to identify relevant articles. Using these databases, we have detected all the studies that have examined the carcinogenic potential of ELF-EMF (EMF ≤ 100 Hz). All articles written in English and French will be reviewed. Two independent reviewers (Dr. Christian Brabant and PhD student Céline Demonceau) are currently performing the study selection.

Prof. O. Bruyère, Dr. C. Brabant, Dr. A. Geerinck, Dr. C. Beaudart, Prof. E. Tirelli, Prof. C. Geuzaine

Exposure to magnetic fields and childhood Leukemia: a systematic review and meta-analysis of case-control and cohort studies
Introduction The association between childhood leukemia and extremely low frequency magnetic fields (ELF-MF) generated by power lines and various electric appliances has been studied extensively during the past forty years. However, the conditions under which ELF-MF represent a risk factor for leukemia are still unclear. Therefore, we have performed a systematic review and meta-analysis to clarify the relation between ELF-MF from several sources and childhood leukemia.
Methods We have systematically searched Medline, Scopus, Cochrane Database of Systematic Review and DARE to identify each article that has examined the relationship between ELF-MF and childhood leukemia. We have performed a global meta-analysis that takes into account the different measures used to assess magnetic field exposure: magnetic flux density measurements (< 0.2 μT vs > 0.2 μT), distances between the child’s home and power lines (> 200 m vs < 200 m) and the wire codings defined by Wertheimer et Leeper in 1979 (low current configuration vs high current configuration, cf. Am J Epidemiol 109, 273-84). Moreover, meta-analyses either based on magnetic flux densities, on proximity to power lines or on wire codings have been performed. The association between electric appliances and childhood leukemia has also been examined.
Results Of the 861 references identified, 39 studies have been included in our systematic review. Our global meta-analysis supports an association between childhood leukemia and ELF-MF (21 studies, OR = 1.24; 95% CI 1.06 – 1.46), an association mainly explained by the studies conducted before 2000 (earlier studies: OR = 1.46; 95% CI 1.20 – 1.77 vs later studies: OR = 1.05; 95% CI 0.88 – 1.26). Our meta-analyses based only on magnetic field measurements indicated that the magnetic flux density threshold associated with childhood leukemia is higher than 0.4 μT (13 studies, > 0.4 μT: OR = 1.47; 95% CI 1.12 – 1.92; acute lymphoblastic leukemia alone: 7 studies, > 0.4 μT: OR = 1.88; 95% CI 1.31- 2.70). Lower magnetic fields were not associated with leukemia (14 studies, 0.1 – 0.2 μT: OR = 1.05; 95% CI 0.88 – 1.24; 0.2 – 0.4 μT: OR = 1.05; 95% CI 0.87 – 1.28). Our meta-analyses based only on distances (5 studies) showed that the estimated summary OR for living within 200 m of power lines and within 50 m of power lines were 0.98 (95 % CI 0.85-1.12) and 1.11 (95% CI 0.81, 1.52), respectively. The OR for living within 50 m of power lines and acute lymphoblastic leukemia analyzed separately was 1.44 (95% CI 0.72-2.88). Our meta-analyses based only on wire codings (5 studies) indicated that the estimated summary OR for the very high current configuration was 1.23 (95% CI 0.72-2.10). Finally, the risk of childhood leukemia was increased after exposure to bedside electric blankets (4 studies, OR = 2.75; 95% CI 1.71 – 4.42; 4 studies) and, to a lesser extent, electric clocks (4 studies, OR = 1.27; 95% CI 1.01 – 1.60).
Conclusion Our results indicate that only ELF-MF higher than 0.4 μT increase the risk of developing leukemia in children, very likely acute lymphoblastic leukemia. Magnetic flux density measurements should be performed if children live within 200 m of overhead power lines to guarantee that they are not exposed to ELF-MF higher than 0.4 μT. However, living more than 200 m away from power lines is likely a safe distance for children not associated with a higher leukemia risk. Children should not use electric blankets that generate magnetic fields higher than 0.4 μT. Finally, “bedside” electric clocks should be located at least one meter away from the bed of the child, because the magnetic flux density generated by electric clocks is lower than 0.4 μT at this distance.

De onderzoekseenheid “Public Health, Epidemiology and Health Economics” heeft een goede expertise in het uitvoeren van systematische reviews en meta-analyses. De eenheid bestaat uit 20 onderzoekers actief in diverse velden gaande van de gezondheid van zwangere vrouwen tot het zich wel bevinden van rusthuisbewoners, inclusief de epidemiologische evaluatie van gezondheidsdeterminanten.

>>> Publicaties over Volksgezondheid

Brabant, Christian, Germain Honvo, Céline Demonceau, Ezio Tirelli, François Léonard, and Olivier Bruyère. “Effects of Extremely Low Frequency Magnetic Fields on Animal Cancer and DNA Damage: A Systematic Review and Meta-Analysis.” Progress in Biophysics and Molecular Biology 195 (March 1, 2025): 137–56. https://doi.org/10.1016/j.pbiomolbio.2024.12.005.

Beaudart, Charlotte ; Rabenda, Véronique ; Bruyère, Olivier (2016) Il n’est jamais trop tard pour apprendre à (bien) lire … La revue systématique. Medi-Sphere 525: 35-38.

Borenstein M, Hedges LV, Higgins JPT, Rothstein HR (2009) Introduction to meta-analysis. New York: Wiley & Sons.

Kabuto M, Nitta H, Yamamoto S, Yamaguchi N, Akiba S, Honda Y, Hagihara J, Isaka K, Saito T, Ojima T, Nakamura Y, Mizoue T, Ito S, Eboshida A, Yamazaki S, Sokejima S, Kurokawa Y, Kubo O (2006) Childhood leukemia and magnetic fields in Japan: a case-control study of childhood leukemia and residential power-frequency magnetic fields in Japan. Int J Cancer 119: 643-50.

Linet MS, Hatch EE, Kleinerman RA, Robison LL, Kaune WT, Friedman DR, Severson RK, Haines CM, Hartsock CT, Niwa S, Wacholder S, Tarone RE (1997) Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med 337: 1-7.

Ioannidis JP (2016) The mass production of redundant, misleading and conflicting systematic reviews and meta-analyses. Milbank Quart 94: 485-514.

Ioannidis JP, Fanelli D, Dunne DD, Goodman SN (2015) Meta-research: evaluation and improvement of research methods and practices. PLOS BIOL 13: e1002264.

Michaelis J, Schüz J, Meinert R, Menger M, Grigat JP, Kaatsch P, Kaletsch U, Miesner A, Stamm A, Brinkmann K, Kärner H (1997) Childhood leukemia and electromagnetic fields: results of a population-based case-control study in Germany. Cancer Causes Control 8: 167-74.

PRISMA website: http://www.bmj.com/content/339/bmj.b2700

Rabenda V, Beaudart C, Bruyère, O (2017) Il n’est jamais trop tard pour apprendre à (bien) lire … La Méta-Analyse. Ortho-Rhumato 15: 27-32.