Potential role of selection bias in the association between childhood leukemia and residential magnetic fields exposure: A population-based assessment

PurposeData from the Northern California Childhood Leukemia Study (NCCLS) were used to assess whether selection bias may explain the association between residential magnetic fields (assessed by wire codes) and childhood leukemia as previously observed in case–control studies.MethodsWiring codes were calculated for participating cases, n = 310; and non-participating cases, n = 66; as well as for three control groups: first-choice participating, n = 174; first-choice non-participating, n = 252; and replacement (non-first choice participating controls), n = 220.ResultsParticipating controls tended to be of higher socioeconomic status than non-participating controls, and lower socioeconomic status was related to higher wire-codes. The odds ratio (OR) for developing childhood leukemia associated with high wire-codes was 1.18 (95% CI: 0.85, 1.64) when all cases were compared to all first-choice controls (participating and non-participating). The OR for developing childhood leukemia in the high current category was 1.43 (95% CI: 0.91, 2.26) when participating cases were compared to first-choice participating controls, but no associations were observed when participating cases were compared to non-participating controls (OR = 1.06, 95% CI: 0.71, 1.57) or to replacement controls (OR = 1.06, 95% CI: 0.71, 1.60).ConclusionsThe observed risk estimates vary by type of control group, and no statistically significant association between wire codes and childhood leukemia is observed in the California population participating in the NCCLS.     

Assessment of non-response bias in a survey of residential magnetic field exposure in Taiwan

We assessed potential non-response bias in obtaining information on residential extremely low-frequency power frequency magnetic field (MF) in Taiwan. All households occupied by children aged less than 7 years in two study districts, one in an urban town and the other in a rural town, were visited and solicited for on-site measurements in late 2003. The initial response rate was only 32% (33/104, urban) and 60% (61/101, rural). In the same season 1 year later, we performed a second survey of those who declined to be measured at the initial survey and successfully measured another 77 residences (50 and 27 for urban and rural districts, respectively). The two districts were selected mainly because the local public health officers were quite willing to assist the initial survey and to inform residents of the second survey. Except for meteorological conditions, the two surveys came up with very similar findings regarding residential characteristics and power facilities surrounding the houses. The mean residential MF for the urban residences was .121 and .140 micro-Tesla (microT) (P = .620) for the two surveys. The corresponding figures for the rural residences were .119 and .115 microT (P = .802). Although limited in its scope, this study tends to indicate that measurement studies of residential MF are less likely to suffer from serious selection bias if sampling is confined within a small district where people have similar socioeconomic characteristics.     

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.     

Contact voltage measured in residences: implications to the association between magnetic fields and childhood leukemia

We measured magnetic fields and two sources of contact current in 36 homes in Pittsfield, MA. The first source, V(P-W), is the voltage due to current in the grounding wire, which extends from the service panel neutral to the water service line. This voltage can cause contact current to flow upon simultaneous contact with a metallic part of the water system, such as the faucet, and the frame of an appliance, which is connected to the panel neutral through the equipment-grounding conductor. The second is V(W-E), the voltage between the water pipe and earth, attributable to ground currents in the water system and magnetic induction from nearby power lines. In homes with conductive water systems and drains, V(W-E) can produce a voltage between the faucet and drain, which may produce contact current into an individual contacting the faucet while immersed in a bathtub. V(P-W) was not strongly correlated to the magnetic field (both log transformed) (r = 0.28; P < 0.1). On the other hand, V(W-E) was correlated to the residential magnetic field (both log transformed) (r = 0.54; P < 0.001), with the highest voltages occurring in homes near high voltage transmission lines, most likely due to magnetic induction on the grounding system. This correlation, combined with both frequent exposure opportunity for bathing children and substantial dose to bone marrow resulting from contact, lead us to suggest that contact current due to V(W-E) could explain the association between high residential magnetic fields and childhood leukemia.     

Potential motion related bias in the worn dosimeter measurements of two childhood leukemia studies

Time averaged field measurements produced by a Positron dosimeter worn by study subjects was the primary method of exposure evaluation in two Canadian studies of childhood leukemia and AC magnetic field exposure. Statistically significant but mutually contradictory results obtained in the two studies, done in different locales but under similar study conditions, have not been explained. This report examines operational features of the Positron meter, including an unanticipated sensitivity to wearer motion. If the convalescent cases studied were less active than their healthy controls, as one might expect, then the meter's characteristic responses to motion, particularly as they would affect case-control distributions above and below the different referent group cutpoints used in the two studies, could help to explain both the unexpected inverse risks reported in the larger study and the unusually high risks reported in the smaller study.     

Evaluating alternative exposure indices in epidemiologic studies on extremely low-frequency magnetic fields

Choosing the right exposure index for epidemiological studies on 50–60 Hz magnetic fields is difficult due to the lack of knowledge about critical exposure parameters for the biological effects of magnetic fields. This paper uses data from a previously published epidemiological investigation on early pregnancy loss (EPL) to study the methods of evaluating the exposure-response relationship of 50 Hz magnetic fields. Two approaches were used. The first approach was to apply generalized additive modeling to suggest the functional form of the relationship between EPL and magnetic field strength. The second approach evaluated the goodness of fit of the EPL data with eight alternative exposure indices: the 24 h average of magnetic field strength, three indices measuring the proportion of time above specified thresholds, and four indices measuring the proportion of time within specified intensity windows. Because the original exposure data included only spot measurements, estimates for the selected exposure indices were calculated indirectly from the spot measurements using empirical nonlinear equations derived from 24 h recordings in 60 residences. The results did not support intensity windows, and a threshold-type dependence on field strength appeared to be more plausible than a linear relationship. In addition, the study produced data suggesting that spot measurements may be used as surrogates for other exposure indices besides the time average field strength. No final conclusions should be drawn from this study alone, but we hope that this exercise stimulates evaluation of alternative exposure indices in other planned and ongoing epidemiological studies. © 1996 Wiley-Liss, Inc.     

Imprecise exposure assessment and the sample size requirements of case-control studies of residential magnetic field exposure and cancer in adults

A computer program simulating case-control studies is described. It is used to estimate the minimum sample size required and to assess how this is affected by imprecise exposure assessment. In particular, the consequences of neglecting measurements of nonresidential exposure in case-control studies of residentially exposed adults are investigated. According to this model, while the consequent loss of power is not as large as was predicted by algebraic methods, it would be unwise to neglect it when planning a study. © 1995 Wiley-Liss, Inc.     

Behavioral effects of long-term exposure to magnetic fields in rats

Male rats and pregnant and nonpregnant female rats of the Wistar strain were sham-exposed or exposed to static (0.49 T) or to extremely low frequency (50 Hz) magnetic fields (0.018 T) 2 h per day for 20 consecutive days. Measures of irritability, exploratory activity, and locomotion were made in that order before and after the 4th, 10th, and 17th 2-h exposures. A reliable decrease in the irritability of rats after repeated exposure to a static or undulating field was found. No significant effects of treatment conditions on open-field behavior and locomotor activity were observed. Pregnancy had no influence on the behavioral end points. These results indicate that irritability of rats may be used as a simple behavioral indicant of mammalian sensitivity to magnetic fields. © 1993 Wiley-Liss. Inc.     

Association of residential magnetic fields with contact voltage

The US National Electrical Code's (NEC) requirement to ground a home's electrical service to the residential water line results in a voltage between the water line and earth, V W-E. The voltage may result from ground return current that flows into the earth via the water line or from inductive effects from other sources of magnetic fields, such as transmission lines. This voltage can, in turn, serve as a source for Vbath, the voltage between the water fixtures and conductive drain pipes sunk into the earth beneath a residence. Vbath can be a source of contact current exposure to a child touching a water fixture while bathing. Previous research has suggested that exposure to these currents could be the basis for the association between power-frequency magnetic fields and childhood leukemia. In this study, we assessed the association between measured Vbath and VW-E with the average spot-measured magnetic field, Bavg, in a sample of 191 single-family residences in the Denver metropolitan area. This area was the source of cases and controls for previous studies of electric and magnetic field (EMF) and childhood cancer. The association of both Vbath and VW-E with Bavg had upward trends across magnetic field strata (<0.1 microT (reference); 0.1-<0.3 microT; and > or = 0.3 microT). In addition, VW-E was associated with Vbath. Without further study, these results cannot be applied to multi-dwelling residences or to electrical systems prevalent in other nations. Nonetheless, when combined with the finding that contact current is a far more plausible candidate than the residential magnetic field for mediating biological effects on the basis of comparative dose to bone marrow, these associations indicate that contact current exposure deserves further study.     

Astrocytoma risk related to job exposure to electric and magnetic fields

To investigate the association between occupational exposure to low-frequency electric and magnetic (EM) fields and risk of brain tumors, a study was performed in Los Angeles County on 272 male adults with primary intracranial gliomas or meningiomas and 272 neighborhood controls. Complete occupational histories were collected. Risk associated with employment for more than 10 years in jobs that are presumed to entail exposure to EM fields was computed for various histological groupings. A nonsignificantly elevated risk of 1.7 was found for gliomas (all types pooled: 95% confidence interval 0.7-4.4), and a nonsignificantly reduced risk of 0.3 (95% confidence interval 0.03-3.2) was found for meningiomas. For astrocytomas, which form a subtype of the gliomas, a significantly elevated risk of 10.3 (95% confidence interval 1.3-80.8) was found; a significant upward trend (P = .01) of tumor incidence with increasing length of employment was observed. Most astrocytoma patients who worked in occupations involving exposure to EM fields were electricians or electrical engineers.     

Decrease in glucose-stimulated insulin secretion following exposure to magnetic fields

We evaluated the effects of extremely low frequency magnetic field (ELFMF) on glucose-stimulated insulin secretion from HIT-T15 cells and investigated the mechanisms of these effects. We demonstrated that exposure to ELFMF at 5mT decreased glucose-stimulated insulin secretion by preventing the increases in cellular adenosine 5'-triphosphate/adenosine 5'-diphosphate, membrane depolarization, and cytosolic free calcium ion concentration. The glucose-induced upregulation of insulin mRNA expression was also attenuated by exposure to ELFMF, although cell viability was not affected. These findings demonstrate the potential of exposure to ELFMF for clinical use as a novel inhibitory method of insulin secretion.     

Early pregnancy loss and exposure to 50-Hz magnetic fields

The possibility of an association of early pregnancy loss (EPL) with residential exposure to ELF magnetic fields was investigated in a case-control study. Eighty-nine cases and 102 controls were obtained from the data of an earlier study aimed at investigating the occurrence of EPL in a group of women attempting to get pregnant. Magnetic-field exposure was characterized by measurements in residences. Strong magnetic fields were measured more often in case than in control residences. In an analysis based on fields measured at the front door, a cutoff score of 0.5 A/m (0.63 μT) resulted in an odds ratio of 5.1 (95% confidence interval 1.0–25). The results should be interpreted cautiously due to the small number of highly exposed subjects and other limitations of the data. © 1993 Wiley-Liss. Inc.     

A scheme for incorporating DC magnetic fields into epidemiological studies of EMF exposure

Experimental data on calcium-ion release in chicken brain tissue suggest that biological effects of electric and magnetic fields (EMFs) are concentrated near certain “active combinations” of DC magnetic field strength and “effective” AC magnetic field frequencies. We hypothesize that active AC/DC combinations may exist and suggest that epidemiologic data, coupled with DC magnetic field measurements, may be used to identify critical exposure conditions. An empirical model is used to calculate these multiple active combinations at any given DC magnetic field strength and to define a rating system that incorporates the proximity of AC magnetic field frequencies generated by electric power lines to the new, computed effective frequencies. Such an exposure score may be useful in investigating correlations of EMF exposure with disease incidence. For 60 Hz and 50 Hz, the highest EMF exposure scores occurred at DC field strengths of 506 mG and 422 mG, respectively. The exposure score contains a factor which may be adjusted to reflect the importance of harmonics of the AC magnetic field as well as of the fundamental frequency. Using this factor, we consider two important special cases consistent with chick brain data: 1) we consider active pairs associated with all detectable harmonics (up to 660 Hz) without regard to relative intensity of the harmonics, and 2) we use the relative intensities of the AC field frequencies to adjust their contribution to the exposure score. © 1993 Wiley-Liss. Inc.     

Present and future magnetic resonance sources of exposure to static fields

This paper considers the exposure of humans to static magnetic fields due to magnetic resonance imaging (MRI) procedures. It briefly introduces the types of magnetic fields associated with MRI. It then discusses trends in the number of people exposed to MRI, the field strength of the magnets used in MRI, and the types of applications of MRI. It also considers the types of staff who are exposed to magnetic fields due to MRI, and the alternative techniques that would be used in the absence of MRI.     

Magnetic field exposure and prognostic factors in childhood leukemia

We examined the association between magnetic field (MF) exposure and the presence of prognostic risk factors among 482 children diagnosed with acute lymphoblastic leukemia (ALL) between 1996 and 2001. Personal 24-h MF measurements were obtained for 412 children; 386 children were included in analyses. There were no trends seen between increasing exposure to MF and the presence of adverse clinical and tumor-specific prognostic factors. Our results suggest that exposure to MF is not associated with the presence of unfavorable cytogenetic abnormalities in leukemic blast cells or with clinical factors at the time of diagnosis that predict poor survival.     

Facility for chronic exposure of rats to ELF magnetic fields

The facility consists of a 12 × 11.5 × 2.4 m high room containing six sets of exposure apparatus and the other equipment necessary to maintain a pathogen-free system. The apparatus sets produced 5 mT (rms), 0.5 mT, or a sham exposure. The apparatus was arranged in the room to minimize the fringing field of the 5 mT set at the sham position. Each set was 3.85 × 1.80 × 0.66 m in outside dimension, containing 24 cages in the magnetically homogeneous region. The apparatus was designed using Harvey's figure-eight-configuration and generated a horizontal sinusoidal alternating field. In order to save electric power, the coil of the apparatus constituted a 50 Hz LC resonance circuit with a condensor bank to which electric power was supplied to compensate losses. Magnetic flux density was kept constant by controlling the coil current. Although mild steel was used in the skeleton of the building, the fringing flux at the sham was as low as 0.1 to 1 μT. Stainless steel was used for ventilating ducts, racks for the cages, cage covers, feeder baskets, and watering nozzles. The homogeneity of the field was measured to be ± 10% in the animal residence area, and food and water consumption was found to be unaffected by the field. At 5 mT, the coil current was 370 A, and the hollow coil was cooled by a stream of 20°C water to prevent both heat and dew on the coil surface. Vibration and acoustic noise was prevented by fiber reinforced plastic framework of the coil. High harmonic distortion was not observed at the output terminal of the coil driver. The facility has operated without trouble for 2 years. © 1993 Wiley-Liss, Inc.     

Destruction of amyloid beta-protein by exposure to weak magnetic fields

It was found that weak magnetic fields (constant 42 microT; variable 0.05 microT; summation of frequencies in the range of 3.58-4.88 Hz) substantially (approximately fourfold) accelerate the hydrolysis of the amyloid beta-protein in aqueous solution. A region of the amyloid beta-protein most sensitive to the action of weak magnetic fields was determined. It is localized between Asp and Ser amino acid residues in positions 7 and 8 of the peptide sequence. It is in this region that the hydrolysis of the molecule of the amyloid beta-protein by the action of magnetic fields predominantly takes place.     

Multigeneration exposure test of Drosophila melanogaster to ELF magnetic fields

Mutations, other than dominant lethals, were accumulated on wild type second chromosomes (+) of Drosophila melanogaster during exposure to 50 Hz sinusoidal alternating magnetic fields of 0.5 or 5 mT (rms) for 40 generations by the Curly/Plum(Cy/Pm) accumulation method. We maintained, for 40 generations under continuous exposure, each (+) chromosome as a heterozygote with (Cy) chromosome. Viability of the (+) chromosome was tested by sib-mating of (Cy/+) male and (Cy/+) female in a culture every 10th generation to obtain the homozygote. Viability indices, defined as twice the ratio of number of (+/+) flies to that of (Cy/+) flies plus 1 in the progeny of the test mating, also were calculated, which equaled 1.00 at the starting point. For the control and 0.5 and 5 mT exposed groups, percent frequencies of recessive lethal lines, defined as a line with (+/+) flies less than 0.3% in the test mating, were, respectively, 1.9, 0.9, and 2.9% (10th), 9.0, 4.9, and 9.5% (20th), 30.3, 22.9, and 30.4% (30th), and 39.9, 32.4, and 43.3% (40th generation). For the control and 0.5 and 5 mT groups, average viability indices, excluding lethals and markedly deleterious, were, respectively, 0.778, 0.796, and 0.752 (20th), 0.704, 0.698, and 0.694 (30th), and 0.669, 0.678, and 0.595 (40th generation). Their decreasing rates were 0.0054, 0.0059, and 0.0078 per generation. No significant difference was detected among the exposure levels in either the recessive lethal mutation frequency or the viability index. Bioelectromagnetics 19:335–340, 1998. © 1998 Wiley-Liss, Inc.