Hypothesis: The risk of childhood leukemia is related to combinations of power-frequency and static magnetic fields

We present a hypothesis that the risk of childhood leukemia is related to exposure to specific combinations of static and extremely-low-frequency (ELF) magnetic fields. Laboratory data from calcium efflux and diatom mobility experiments were used with the gyromagnetic equation to predict combinations of 60 Hz and static magnetic fields hypothesized to enhance leukemia risk. The laboratory data predicted 19 bands of the static field magnitude with a bandwidth of 9.1 μT that, together with 60 Hz magnetic fields, are expected to have biological activity. We then assessed the association between this exposure metric and childhood leukemia using data from a case-control study in Los Angeles County. ELF and static magnetic fields were measured in the bedrooms of 124 cases determined from a tumor registry and 99 controls drawn from friends and random digit dialing. Among these subjects, 26 cases and 20 controls were exposed to static magnetic fields lying in the predicted bands of biological activity centered at 38.0 μT and 50.6 μT. Although no association was found for childhood leukemia in relation to measured ELF or static magnetic fields alone, an increasing trend of leukemia risk with measured ELF fields was found for subjects within these static field bands (P for trend = 0.041). The odds ratio (OR) was 3.3 [95% confidence interval (CI) = 0.4–30.5] for subjects exposed to static fields within the derived bands and to ELF magnetic field above 0.30 μT (compared to subjects exposed to static fields outside the bands and ELF magnetic fields below 0.07 μT). When the 60 Hz magnetic fields were assessed according to the Wertheimer-Leeper code for wiring configurations, leukemia risks were again greater with the hypothesized exposure conditions (OR = 9.2 for very high current configurations within the static field bands: 95% CI = 1.3–64.6). Although the risk estimates are based on limited magnetic field measurements for a small number of subjects, these findings suggest that the risk of childhood leukemia may be related to the combined effects of the static and ELF magnetic fields. Further tests of the hypothesis are proposed. © 1995 Wiley-Liss, Inc.     

Extremely low-frequency magnetic fields of transformers and possible biological and health effects

Physiological processes in organisms can be influenced by extremely low-frequency (ELF) electromagnetic energy. Biological effect studies have great importance; as well as measurement studies since they provide information on the real exposure situations. In this study, the leakage magnetic fields around a transformer were measured in an apartment building in Küçükçekmece, Istanbul, and the measurement results were evaluated with respect to the international exposure standards. The transformer station was on the bottom floor of a three-floor building. It was found that people living and working in the building were exposed to ELF magnetic fields higher than the threshold magnetic field value of the International Agency for Research on Cancer (IARC). Many people living in this building reported health complaints such as immunological problems of their children. There were child-workers working in the textile factories located in the building. Safe distances or areas for these people should be recommended. Protective measures could be implemented to minimize these exposures. Further residential exposure studies are needed to demonstrate the exposure levels of ELF magnetic fields. Precautions should, therefore, be taken either to reduce leakage or minimize the exposed fields. Shielding techniques should be used to minimize the leakage magnetic fields in such cases.     

Children's exposure to magnetic fields produced by U.S. television sets used for viewing programs and playing video games

Two epidemiologic studies have reported increased risk of childhood leukemia associated with the length of time children watched television (TV) programs or played video games connected to TV sets. To evaluate magnetic field exposures resulting from these activities, the static, ELF, and VLF magnetic fields produced by 72 TV sets used by children to watch TV programs and 34 TV sets used to play video games were characterized in a field study conducted in Washington DC and its Maryland suburbs. The resulting TV-specific magnetic field data were combined with information collected through questionnaires to estimate the magnetic field exposure levels associated with TV watching and video game playing. The geometric means of the ELF and VLF exposure levels so calculated were 0.0091 and 0.0016 microT, respectively, for children watching TV programs and 0.023 and 0.0038 microT, respectively, for children playing video games. Geometric means of ambient ELF and VLF levels with TV sets turned off were 0.10 and 0.0027 microT, respectively. Summed over the ELF frequency range (6-3066 Hz), the exposure levels were small compared to ambient levels. However, in restricted ELF frequency ranges (120 Hz and 606-3066 Hz) and in the VLF band, TV exposure levels were comparable to or larger than normal ambient levels. Even so, the strengths of the 120 Hz or 606-3066 Hz components of TV fields were small relative to the overall ambient levels. Consequently, our results provide little support for a linkage between childhood leukemia and exposure to the ELF magnetic fields produced by TV sets. Our results do suggest that any future research on possible health effects of magnetic fields from television sets might focus on the VLF electric and magnetic fields produced by TV sets because of their enhanced ability relative to ELF fields to induce electric currents.     

Childhood leukemia--risk factors and the need for an interdisciplinary research agenda

The International Agency for Research on Cancer (IARC) has classified high as well as low-frequency fields as “possibly carcinogenic to humans” (Group 2B). For high frequency fields the recent assessment is based mainly on weak positive associations described in some epidemiological studies between glioma and acoustic neuroma and the use of mobile and other wireless phones. Also for lowfrequency fields the evidence is based on epidemiological findings revealing a statistic association between childhood leukemia (CL) and low-level magnetic fields. The basic findings are already 10 years old. They have since been supported by further epidemiological studies. However, the knowledge on the main/crucial question of causality has not improved. This fact and in addition the small, but statistically significant increased incidence of CL in the surrounding of German nuclear power plants have motivated the German Office for Radiation Protection (BfS) to work toward a better understanding of the main causes of CL. A long-term strategic research agenda has been developed which builds on an interdisciplinary, international network and aims at clarifying the aetiology of childhood acute lymphoblastic leukemia.     

Novel ETV6‐RUNX1 Mouse Model to Study the Role of ELF‐MF in Childhood B‐Acute Lymphoblastic Leukemia: a Pilot Study

Exposure to extremely low‐frequency magnetic fields (ELF‐MFs) has been classified by the International Agency for Research on Cancer (IARC) as “possibly carcinogenic to humans,” based on limited scientific evidence concerning childhood leukemia. This assessment emphasized the lack of appropriate animal models recapitulating the natural history of this disease. Childhood B‐cell acute lymphoblastic leukemia (B‐ALL) is the result of complex interactions between genetic susceptibility and exposure to exogenous agents. The most common chromosomal alteration is the ETV6‐RUNX1 fusion gene, which confers a low risk of developing the malignancy by originating a preleukemic clone requiring secondary hits for full‐blown disease to appear. To develop potential prophylactic interventions, we need to identify the environmental triggers of the second hit. Recently, we generated a B‐ALL mouse model of the human ETV6‐RUNX1⁺ preleukemic state. Here, we present the results from the ARIMMORA pilot study, obtained by exposing 34 Sca1‐ETV6‐RUNX1 mice (vs. 27 unexposed) to a 50 Hz magnetic field of 1.5 mT with both fundamental and harmonic content, with an on/off cycle of 10 min/5 min, for 20 h/day, from conception until 3 months of age. Mice were monitored until 2 years of age and peripheral blood was periodically analyzed by flow cytometry. One of the exposed mice developed B‐ALL while none of the non‐exposed did. Although the results are statistically non‐significant due to the limited number of mice used in this pilot experiment, overall, the results show that the newly developed Sca1‐ETV6‐RUNX1 mouse can be successfully used for ELF‐MF exposure studies about the etiology of childhood B‐ALL. Bioelectromagnetics. 2019;40:343–353. © 2019 Bioelectromagnetics Society.     

Electromagnetic fields and epidemiology: An overview inspired by the fourth course at the International School of Bioelectromagnetics

The fourth course at the International School of Bioelectromagnetics addressed various aspects of the epidemiology of exposure to electromagnetic fields (EMF). In this overview, inspired by the lectures and the discussions among participants, we summarize current knowledge on exposure to EMF and disease risk, with emphasis on studies of use of mobile phones and brain tumours and exposure to power lines and childhood leukaemia. Sources of bias and error hamper straightforward conclusions in some areas and, in order to move forward, improvements in study design and exposure assessment are necessary. The scientific evidence available to date on possible long‐term effects from exposure to ELF and RF fields is not strong enough to revise current protection limits based on the known acute effects of such exposures. Precautionary measures may be considered to reduce ELF exposure of children or exposure to RF during mobile phone use, keeping in mind that it is unclear whether they involve any preventive benefit. Possible health effects from mobile phone use in adults and in children should be investigated further by prospective epidemiological studies with improved exposure assessment and brain tumour incidence rates should be monitored. Further studies on the relation between childhood leukaemia and ELF magnetic fields would be worthwhile if they focus on heavily exposed groups and attempt to minimize possible selection bias. In conclusion, epidemiological studies conducted with appropriate diligence can play a key role in finding the answers. Bioelectromagnetics 30:511–524, 2009. © 2009 Wiley‐Liss, Inc.     

ELF magnetic fields: animal studies, mechanisms of action

Animal studies can contribute to addressing the issue of possible greater health risk for children exposed to 50–60 Hz extremely low frequency (ELF) magnetic fields (MFs), mostly in terms of teratological effects and cancer.Teratology has been extensively studied in animals exposed to ELF MFs but experiments have not established adverse developmental effects.Childhood leukaemia has been the only cancer consistently reported in epidemiological studies as associated with exposure to ELF MFs. This association has been the basis for the classification as “possibly carcinogenic to humans” by the International Agency for Research on Cancer in 2002. Animal experiments have provided only limited support for these epidemiological findings. However, none but one study used an animal model for acute lymphoblastic leukaemia (ALL), the main form of childhood leukaemia, and exposures to ELF MFs were not carried out over the whole pregnancy period, when the first hit of ALL is assumed to occur.Moreover, there are no generally accepted biophysical mechanisms that could explain carcinogenic effects of low-level MFs. The radical pair mechanism and related cryptochromes (CRY) molecules have recently been identified in birds and other non-mammalian species, as a sensor of the geomagnetic field, involved in navigation. The hypothesis has to be tested in mammalian models. CRY, which is part of the molecular circadian clock machinery, is a ubiquitous protein likely to be involved in cancer cell growth and DNA repair.In summary, we now have some clues to test for a better characterization of the interaction between ALL and ELF MFs exposure.     

Magnetic fields produced by hand held hair dryers, stereo headsets, home sewing machines, and electric clocks.

A recent epidemiologic study reported associations between leukemia risk in children and their personal use of television (TV) sets, hair dryers, and stereo headsets, and the prenatal use by their mothers of sewing machines. To provide exposure data to aid in the interpretation of these findings, extremely and very low frequency (ELF and VLF) magnetic fields produced by a sample of each type of appliance were characterized in a field study of volunteers conducted in Washington DC and its Maryland suburbs. Questionnaire data regarding children's or mothers' patterns of usage of each type of appliance were also collected. ELF magnetic fields measured 10 cm from the nozzles of hair dryers were elevated over the ambient by a mean factor of 17 when these devices were in use. Fields near headsets being used to listen to music were not distinguishable from ambient levels except at frequencies below and well above 60 Hz and, even then, field levels were < 0.01 microT. Home sewing machines produced ELF magnetic fields that were elevated by a factor of 2.8 over ambient levels at the front surfaces of the lower abdomens of mothers. Estimated mean daily times of usage of hair dryers, stereo headsets, and sewing machines were 2.6, 19, and 17 minutes, respectively. These data and previously published data on TV sets, do not provide a consistent picture of increased (or decreased) leukemia risk in relation to increasing peak or time weighted average (TWA) ELF magnetic field exposure. The data could, however, conceivably be compatible with some more complex biophysical model with unknown properties. Overall, the results of this study provide little evidence supporting the hypothesis that peak or TWA ELF magnetic fields produced by appliances are causally related to the risk of childhood leukemia in children.     

Residential magnetic fields predicted from wiring configurations: I. Exposure model.

A physically based model for residential magnetic fields from electric transmission and distribution wiring was developed to reanalyze the Los Angeles study of childhood leukemia by London et al. For this exposure model, magnetic field measurements were fitted to a function of wire configuration attributes that was derived from a multipole expansion of the Law of Biot and Savart. The model parameters were determined by nonlinear regression techniques, using wiring data, distances, and the geometric mean of the ELF magnetic field magnitude from 24-h bedroom measurements taken at 288 homes during the epidemiologic study. The best fit to the measurement data was obtained with separate models for the two major utilities serving Los Angeles County. This model's predictions produced a correlation of 0.40 with the measured fields, an improvement on the 0.27 correlation obtained with the Wertheimer-Leeper (WL) wire code. For the leukemia risk analysis in a companion paper, the regression model predicts exposures to the 24-h geometric mean of the ELF magnetic fields in Los Angeles homes where only wiring data and distances have been obtained. Since these input parameters for the exposure model usually do not change for many years, the predicted magnetic fields will be stable over long time periods, just like the WL code. If the geometric mean is not the exposure metric associated with cancer, this regression technique could be used to estimate long-term exposures to temporal variability metrics and other characteristics of the ELF magnetic field which may be cancer risk factors.     

Microwave electromagnetic field regulates gene expression in T-lymphoblastoid leukemia CCRF-CEM cell line exposed to 900 MHz

Electric, magnetic, and electromagnetic fields are ubiquitous in our society, and concerns have been expressed regarding possible adverse effects of these exposures. Research on Extremely Low-Frequency (ELF) magnetic fields has been performed for more than two decades, and the methodology and quality of studies have improved over time. Studies have consistently shown increased risk for childhood leukemia associated with ELF magnetic fields. There are still inadequate data for other outcomes. More recently, focus has shifted toward Radio Frequencies (RF) exposures from mobile telephony. There are no persuasive data suggesting a health risk, but this research field is still immature with regard to the quantity and quality of available data. This technology is constantly changing and there is a need for continued research on this issue. To investigate whether exposure to high-frequency electromagnetic fields (EMF) could induce adverse health effects, we cultured acute T-lymphoblastoid leukemia cells (CCRF-CEM) in the presence of 900?MHz MW-EMF generated by a transverse electromagnetic (TEM) cell at short and long exposure times. We evaluated the effect of high-frequency EMF on gene expression and we identified functional pathways influenced by 900?MHz MW-EMF exposure.     

Residential magnetic fields predicted from wiring configurations: II. Relationships To childhood leukemia.

Case-control data on childhood leukemia in Los Angeles County were reanalyzed with residential magnetic fields predicted from the wiring configurations of nearby transmission and distribution lines. As described in a companion paper, the 24-h means of the magnetic field's magnitude in subjects' homes were predicted by a physically based regression model that had been fitted to 24-h measurements and wiring data. In addition, magnetic field exposures were adjusted for the most likely form of exposure assessment errors: classic errors for the 24-h measurements and Berkson errors for the predictions from wire configurations. Although the measured fields had no association with childhood leukemia (P for trend=.88), the risks were significant for predicted magnetic fields above 1.25 mG (odds ratio=2.00, 95% confidence interval=1.03-3.89), and a significant dose-response was seen (P for trend=.02). When exposures were determined by a combination of predictions and measurements that corrects for errors, the odds ratio (odd ratio=2.19, 95% confidence interval=1.12-4.31) and the trend (p =.007) showed somewhat greater significance. These findings support the hypothesis that magnetic fields from electrical lines are causally related to childhood leukemia but that this association has been inconsistent among epidemiologic studies due to different types of exposure assessment error. In these data, the leukemia risks from a child's residential magnetic field exposure appears to be better assessed by wire configurations than by 24-h area measurements. However, the predicted fields only partially account for the effect of the Wertheimer-Leeper wire code in a multivariate analysis and do not completely explain why these wire codes have been so often associated with childhood leukemia. The most plausible explanation for our findings is that the causal factor is another magnetic field exposure metric correlated to both wire code and the field's time-averaged magnitude.     

The relationship between residential magnetic fields and contact voltage: a pooled analysis

It has been suggested that residential exposure to contact currents may be more directly associated with the potential for an increased risk of leukemia in childhood than magnetic fields. Contact current exposure occurs when a child contacts a bathtub's water fixtures, which are usually contiguous with a residence's electrical ground, and when the drainpipe is conductive. The Northern California Childhood Leukemia Study (NCCLS) is the only epidemiological study known to address whether contact current may confound the reported association between residential magnetic fields and childhood leukemia. The study contributed contact voltage and magnetic-field data for over 500 residences of leukemia cases and control children. We combined these data with the results of previous measurement studies of contact voltage in other communities to conduct an analysis of the relationship of magnetic fields with contact voltage for a total sample of 702 residences. The Spearman correlation of magnetic field with contact voltage was 0.29 (Spearman, P < 0.0001). Magnetic-field and contact voltage data were both divided into tertiles, with an upper magnetic-field cutpoint of 0.3 μT suggested by values used in epidemiological results and an upper contact voltage cutpoint of 60 mV based on dosimetric considerations. Expressed as an exposure odds ratios (EOR), we report an association of contact voltage with magnetic fields of 15.1 (95% CI 3.6-61) as well as a statistically significant positive trend across magnetic-field strata (EOR of 4.2 per stratum with 95% CI 2.4-7.4). The associations appear to be large enough to support the possibility that contact current could be responsible for the association of childhood leukemia with magnetic fields.     

Childhood leukemia, electric and magnetic fields, and temporal trends

During the past 25 years concern has been raised about the possible health effects of extremely low frequency (ELF) electric and magnetic fields (EMFs), particularly regarding childhood leukemia. Comparison of changes in electricity consumption (a surrogate for exposure) to changes in childhood-leukemia rates, known as ecologic correlation, have been used to argue both for and against the association between magnetic fields and childhood leukemia. In this paper we explore what can be learned from such an ecologic approach. We first examine separately the evidence on trends in exposure to EMFs and on trends in leukemia rates, and then compare the two. Both incidence rates and exposures have increased, but there are so many approximations and assumptions involved in connecting the two trends that we cannot regard the ecologic evidence as providing any meaningful evidence for or against a causal link.     

Exposure to extremely low-frequency magnetic fields and the risk of childhood cancer: update of the epidemiological evidence

There is an ongoing scientific controversy whether the observed association between exposure to residential extremely low-frequency magnetic fields (ELF-MF) and the risk of childhood leukaemia observed in epidemiological studies is causal or due to methodological shortcomings of those studies. Recent pooled analysis confirm results from previous studies, namely an approximately two-fold risk increase at ELF-MF exposures ≥0.4 μT, and demonstrate consistency of studies across countries, with different design, different methods of exposure assessment, and different systems of power transmission and distribution. On the other hand, recent pooled analyses for childhood brain tumour show little evidence for an association with ELF-MF, also at exposures ≥0.4 μT. Overall, the assessment that ELF-MF are a possible carcinogen and may cause childhood leukaemia remains valid. Ongoing research activities, mainly experimental and few new epidemiological studies, hopefully provide additional insight to bring clarity to a research area that has remained inconclusive.     

Epidemiology of childhood leukemia in the presence and absence of Down syndrome

Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children.We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia.     

Effects of ELF magnetic fields on protein expression profile of human breast cancer cell MCF7

A case-control study in 1979 on electrical wiring configurations and childhood leukemia had stimulated interest in the issue that extremely low frequency magnetic fields (ELF MF) may have harmful biologi-cal effects especially on the incidence of human can-cer[1]. Since then, a large number of studies have been conducted to follow up this important result[2]. The majority of these studies indicate a weak association between exposure to 50―60 Hz ELF MF and the in-cidence of cancer; however…     

Effects of ELF magnetic fields on protein expression profile of human breast cancer cell MCF7

Extremely Low Frequency Magnetic Fields (ELF MF) has been considered as a “possible human carcinogen” by International Agency for Research on Cancer (IARC) while credible mechanisms of its carcinogenicity remain unknown. In this study, a proteomics approach was employed to investigate the changes of protein expression profile induced by ELF MF in human breast cancer cell line MCF7, in order to determine ELF MF-responsive proteins. MCF7 cells were exposed to 50 Hz, 0.4 mT ELF MF for 24 h and the changes of protein profile were examined using two dimensional electrophoresis. Up to 6 spots have been statistically significantly altered (their expression levels were changed at least 5 fold up or down) compared with sham-exposed group. 19 ones were only detected in exposure group while 19 ones were missing. Three proteins were identified by LC-IT Tandem MS as RNA binding protein regulatory subunit Proteasome subunit beta type 7 precursor and Translationally Controlled Tumor Protein. Our finding showed that 50 Hz, 0.4 mT ELF MF alternates the protein profile of MCF7 cell and may affect many physiological functions of normal cell and 2-DE coupled with MS is a promising approach to elucidating cellular effects of electromagnetic fields.     

Exposure to electrical contact currents and the risk of childhood leukemia

The objectives of this study were to examine the association between contact current exposure and the risk of childhood leukemia and to investigate the relationship between residential contact currents and magnetic fields. Indoor and outdoor contact voltage and magnetic-field measurements were collected for the diagnosis residence of 245 cases and 269 controls recruited in the Northern California Childhood Leukemia Study (2000-2007). Logistic regression techniques produced odds ratios (OR) adjusted for age, sex, Hispanic ethnicity, mother's race and household income. No statistically significant associations were seen between childhood leukemia and indoor contact voltage level [exposure ≥90th percentile (10.5 mV): OR = 0.83, 95% confidence interval (CI): 0.45, 1.54], outdoor contact voltage level [exposure ≥90th percentile (291.2 mV): OR = 0.89, 95% CI: 0.48, 1.63], or indoor magnetic-field levels (>0.20 μT: OR = 0.76, 95% CI: 0.30, 1.93). Contact voltage was weakly correlated with magnetic field; correlation coefficients were r = 0.10 (P = 0.02) for indoor contact voltage and r = 0.15 (P = 0.001) for outdoor contact voltage. In conclusion, in this California population, there was no evidence of an association between childhood leukemia and exposure to contact currents or magnetic fields and a weak correlation between measures of contact current and magnetic fields.     

Childhood leukemia and residential magnetic fields: Are pooled analyses more valid than the original studies?

The association seen in epidemiological studies between childhood leukemia and magnetic field strength in the child's home has been very important in influencing reviews of international groups and standard setting organizations. This association is usually based on the results of two published pooled analyses, which use definitions of exposure that differ from those of some the original studies. However, the results and conclusions of the pooled analyses differ from those of the three largest recent studies, which have the most sophisticated methodology and together account for the majority of the exposed cases at high exposure levels in the pooled analyses. These recent studies, using the exposure methods and the cut-off levels set a priori, each concluded that there was little evidence of any association. The pooled analyses, using different exposure measures and different cut-offs, conclude that an association exists at high exposure levels. It is not clear if the results of the pooled analysis are more valid than those of the recent major studies, although this has been often assumed in influential reviews.     

Extremely low frequency electric fields and cancer: Assessing the evidence

Much of the research and reviews on extremely low frequency (ELF) electric and magnetic fields (EMFs) have focused on magnetic rather than electric fields. Some have considered such focus to be inappropriate and have argued that electric fields should be part of both epidemiologic and laboratory work. This paper fills the gap by systematically and critically reviewing electric‐fields literature and by comparing overall strength of evidence for electric versus magnetic fields. The review of possible mechanisms does not provide any specific basis for focusing on electric fields. While laboratory studies of electric fields are few, they do not indicate that electric fields should be the exposure of interest. The existing epidemiology on residential electric‐field exposures and appliance use does not support the conclusion of adverse health effects from electric‐field exposure. Workers in close proximity to high‐voltage transmission lines or substation equipment can be exposed to high electric fields. While there are sporadic reports of increase in cancer in some occupational studies, these are inconsistent and fraught with methodologic problems. Overall, there seems little basis to suppose there might be a risk for electric fields, and, in contrast to magnetic fields, and with a possible exception of occupational epidemiology, there seems little basis for continued research into electric fields. Bioelectromagnetics 31:89–101, 2010. © 2009 Wiley‐Liss, Inc.