Residential Magnetic Fields, Light-at-Night, and Nocturnal Urinary 6

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<ul><li><p>591</p><p>American Journal of</p><p>EPIDEMIOLOGYCopyright 2001 by the Johns Hopkins University</p><p>Bloomberg School of Public Health</p><p>Sponsored by the Society for Epidemiologic Research</p><p>Published by Oxford University Press</p><p>Volume 154</p><p>Number 7</p><p>October 1, 2001</p><p>Magnetic Fields, Light-at-Night, and Melatonin Davis et al.ORIGINAL CONTRIBUTIONS</p><p>Residential Magnetic Fields, Light-at-Night, and Nocturnal Urinary 6-Sulfatoxymelatonin Concentration in Women</p><p>Scott Davis,1,2 William T. Kaune,3 Dana K. Mirick,1 Chu Chen,1 and Richard G. Stevens4</p><p>Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing the normal nocturnal risein melatonin. This 19941996 Washington State study investigated whether such exposure was associated withlower nocturnal urinary concentration of 6-sulfatoxymelatonin in 203 women aged 2074 years with no historyof breast cancer. Each woman was interviewed and provided data on the following for a 72-hour period at twodifferent seasons of the year: 1) magnetic field and ambient light measured every 30 seconds in her bedroom,2) personal magnetic field measured at 30-second intervals, and 3) complete nighttime urine samples on threeconsecutive nights. Lower nocturnal urinary 6-sulfatoxymelatonin level was associated with more hours ofdaylight, older age, higher body mass index, current alcohol consumption, and current use of medicationsclassified as beta blockers, calcium channel blockers, or psychotropics. After adjustment for these factors, higherbedroom magnetic field level was associated with significantly lower urinary concentration of 6-sulfatoxymelatonin during the same night, primarily in women who used these medications and during times ofthe year with the fewest hours of darkness. These results suggest that exposure to nighttime residential 60-Hzmagnetic fields can depress the normal nocturnal rise in melatonin. Am J Epidemiol 2001;154:591600.</p><p>breast neoplasms; carcinogens, environmental; circadian rhythm; electricity; electromagnetic fields; melatonin</p><p>Received for publication July 6, 2000, and accepted for publica-tion December 20, 2000.</p><p>Abbreviation: BMI, body mass index.1 Program in Epidemiology, Division of Public Health Sciences,</p><p>Fred Hutchinson Cancer Research Center, Seattle, WA.2 Department of Epidemiology, School of Public Health and</p><p>Community Medicine, University of Washington, Seattle, WA.3 EM Factors, Richland, WA.4 Department of Community Medicine, University of Connecticut</p><p>Health Center, Farmington, CT.Reprint requests to Dr. Scott Davis, Fred Hutchinson Cancer</p><p>Research Center, 1100 Fairview Avenue North MP-474, P.O. Box19024, Seattle, WA 98109-1024 (e-mail:</p><p>It has been suggested that exposure to 60-Hz magneticfields may increase the risk of breast cancer by suppressingthe normal nocturnal rise in melatonin production andrelease (1), thereby resulting in increased levels of circulat-ing estrogen. Several lines of inquiry have been pursued toinvestigate a possible link between pineal function, circulat-ing estrogen level, and breast cancer risk (summarized byStevens and Davis and by Brainard et al. (2, 3)). Other thanlimited evidence that blood melatonin levels are reduced inhuman volunteers exposed to magnetic fields (4), there have</p><p>been few studies of the effect of magnetic field exposure onpineal function in humans. Although some results fromexperimental and occupational studies suggest that nocturnalmelatonin levels can be reduced by exposure to magneticfields, the evidence thus far is inconsistent and incomplete(510). More importantly, it remains unknown whether suchexposures can alter the endogenous hormonal environmentin women in a manner that might be important in the etiol-ogy of breast cancer. Therefore, the present study wasundertaken in 19941996 to investigate, for the first knowntime in women, whether exposure to magnetic fields and/orlight-at-night is associated with lower nocturnal concentra-tion of the primary metabolite of melatonin found in theurine (6-sulfatoxymelatonin).</p><p>MATERIALS AND METHODS</p><p>Study participants</p><p>Participants were women aged 2074 years selected froma group of 591 women in King and Snohomish counties inWashington State who participated as controls in a case-control study of breast cancer and exposure to electromag-</p><p>Downloaded from gueston 13 February 2018</p></li><li><p>592 Davis et al.</p><p>Am J Epidemiol Vol. 154, No. 7, 2001</p><p>netic fields (11). The women initially were identified by ran-dom digit dialing (12). A sample was selected to provideapproximately equal representation of the highest and low-est bedroom magnetic field exposures. Of the 31 womenstill living in homes classified as Very High CurrentConfiguration according to the scheme developed byWertheimer and Leeper (13) to approximate exposuresinside a residence on the basis of external wiring configura-tions, 26 (84 percent) agreed to participate. Each of theremaining 556 potentially eligible women was ordered bythe mean magnetic field level measured in her bedroom overa 48-hour continuous period during her participation in thecase-control study. Eighty-three (82 percent) of the 101 eli-gible women who had the highest measured exposures and94 (85 percent) of the 110 eligible women who had the low-est measured exposures agreed to participate. The institu-tional review board approved the protocol for contactingpotential participants and the manner in which informedconsent was obtained.</p><p>Data collection and laboratory methods</p><p>Data collection consisted of the elements described intable 1 for a 72-hour measurement period. The entire proto-col was repeated approximately 3 or 6 months later, basedon random assignment, to provide measurements in differ-ent seasons of the year. This study design made it possibleto investigate the effects of different lengths of daily dark-ness on any potential association between magnetic field</p><p>exposure and urinary 6-sulfatoxymelatonin level. The studytook place over approximately 14 months.</p><p>The volume of urine was determined, and each samplewas assayed for creatinine concentration based on a kineticmodification of the Jaffe reaction using the Roche Reagentfor Creatinine (Roche Diagnostic Systems, Nutley, NewJersey). Urinary concentrations of the primary metabolite ofmelatonin, 6-sulfatoxymelatonin, were determined by usingcommercially available radioimmunoassay kits (CIDtechResearch Inc., Mississauga, Ontario, Canada). The assaywas run in duplicate with 500 l of diluted sample. Each runincluded the kit control provided by the manufacturer and anin-house control using a urine sample provided by a volunteer at the beginning of the study was used. Assay sen-sitivity was 0.5 ng/ml urine, and intra- and interassay per-cent coefficients of variation were approximately 9 and 13percent, respectively.</p><p>Statistical methods</p><p>Nine exposure variables were defined prior to analysis tocharacterize a participants exposure to magnetic fields. Thefollowing three reflected exposure to magnetic fields in thebedroom at night: 1) mean nighttime bedroom magneticfield exposure, 2) proportion of nighttime bedroom mag-netic field measurements 0.2 T, and 3) short-term vari-ability in the bedroom magnetic field. Nighttime wasdefined for each subject and each night as the time periodbetween the last void before going to bed and the first void</p><p>TABLE 1. Data elements studied to determine a possible association between exposure to magneticfields and/or light-at-night and urinary 6-sulfatoxymelatonin concentration, Washington State, 19941996</p><p>In-person interview</p><p>Personal magnetic field exposure*</p><p>Bedroom magnetic field exposure*</p><p>Ambient light*</p><p>Urine sample</p><p>Protocol adherence form</p><p>Patterns of electric blanket useCurrent medication useUpdate of personal habits since case-control study</p><p>EMDEX Lite meterBroadband (40800 Hz) x, y, and z orthogonal components of </p><p>fieldMeasurements at 30-second intervals on a 24-hour basisDiary of activities in 30-minute time segments</p><p>EMDEX II meterBroadband (40800 Hz) and harmonics (100800 Hz)Measurements at 30-second intervals during the nightMeter placed on floor near head of bed where magnetic field</p><p>is within 0.05 T of field on pillow</p><p>Commercial light sensorMeasured at 30-second intervals at head of bed during the night</p><p>Complete nighttime urine sample on 3 consecutive nights</p><p>Documented subjects night and any problems with urinecollection</p><p>Element Description</p><p>* All meters were calibrated prior to the start of the study and periodically on a regular basis thereafter. Enertech Consultants, Campbell, California. Graseby Electronics, Orlando, Florida. Participants were instructed to void their bladder just prior to retiring; any urine excreted after that time,</p><p>including the first morning void just after rising, was collected.</p><p>Downloaded from gueston 13 February 2018</p></li><li><p>Magnetic Fields, Light-at-Night, and Melatonin 593</p><p>Am J Epidemiol Vol. 154, No. 7, 2001</p><p>the next morning. Mutually exclusive 10-minute timeblocks were used to group exposure measurements. A statis-tic (Y) was computed to characterize short-term variabilityin the bedroom magnetic field, as follows:</p><p>where Bk, k = 1, 2, , 20 are the 20 values of the measuredmagnetic field recorded at 30-second intervals during a 10-</p><p>minute time period. This statistic, when divided by (i.e., the number of measurement intervals 1), is equal tothe rate-of-change metric introduced by Yost (14). Thebedroom variability statistic was defined as the average ofall 10-minute Y statistics during the nighttime period.</p><p>Three variables reflected personal exposure to magneticfields on a continual (24-hour) basis: 1) mean 24-hour per-sonal magnetic field exposure, 2) proportion of 24-hour per-sonal magnetic field measurements 0.2 T, and 3) short-term variability in the personal magnetic field (defined asabove). In addition, one variable was constructed to reflectthe wire code configuration assigned to each participantsresidence according to the scheme developed by Wertheimerand Leeper (13). Two variables were defined to characterizeexposure to light-at-night: 1) proportion of nighttime bed-room light measurements 10 lux and 2) number of timesthe subject reported getting up and turning on a light.</p><p>Additional factors known or suspected to affect mela-tonin levels were specified a priori for use in covariateadjustment. Primary covariates were defined as those wellestablished from previous research to affect melatonin lev-els and included participant age, menopausal status, andduration of darkness. Participants were classified as pre-menopausal if they reported regular or irregular periods,did not use hormone replacement therapy, and had notundergone a hysterectomy with oophorectomy; otherwise,they were classified as postmenopausal. Fifteen partici-pants were considered indeterminate according to thisdefinition and were classified as premenopausal if aged2 percent of the total vol-ume were deemed unusable (n = 37 samples, 21 in session 1and 16 in session 2). There were eight samples from fivesubjects whose concentrations of 6-sulfatoxymelatonin werebelow the detectable limits of the assay (0.5 ng mela-tonin/ml urine). These samples were assigned one half thevalue of the detectable limit of the assay before being nor-malized to creatinine level. Samples from both measure-ment sessions for one participant and one measurement ses-</p><p>Downloaded from gueston 13 February 2018</p></li><li><p>594 Davis et al.</p><p>Am J Epidemiol Vol. 154, No. 7, 2001</p><p>sion for two participants were excluded from the analysisbecause they reported using melatonin supplements at leastonce during the measurement period, which resulted in 6-sulfatoxymelatonin levels that were elevated more than 100times over the unsupplemented values.</p><p>Table 2 shows the distributions of two of the three pri-mary covariates and the secondary covariates. The distribu-tion of number of hours of daily darkness was slightly U-shaped (data not shown), reflecting a slightly greaternumber of total sample days occurring at the extremes of therange of daily darkness (8.0 hours at the summer solsticeand 15.6 hours at the winter solstice).</p><p>Urinary 6-sulfatoxymelatonin concentration</p><p>A total of 1,106 nocturnal urine samples were available foranalysis. The distribution of urinary 6-sulfatoxymelatoninconcentration was right skewed, meaning that the majority ofthe measurements were at the low end of the scale (mean,19.3 ng/mg creatinine; standard deviation, 12.8). The concen-</p><p>tration varied somewhat according to the season of the year;each season was defined as the 3 months centered on therespective equinox or solstice. Concentrations were highest inwinter (mean, 22.5 ng/mg creatinine) and lowest in summer(mean,16.8 ng/mg creatinine). Spring and fall values wereintermediate (means, 20.1 and 18.1, respectively). Urinary 6-sulfatoxymelatonin concentrations were highly and signifi-cantly correlated from day to day within each measurementsession (Spearmans rank correlation coefficients: 0.90 and0.85, respectively for the two sessions; p &lt; 0.0001 for both)as well as between measurement sessions (Spearmans rankcorrelation coefficient: 0.75; p &lt; 0.0001).</p><p>Measures of exposure to magnetic fields and light-at-night</p><p>Table 3 summarizes the measures of exposure to mag-netic fields and light-at-night. Mean nighttime bedroommagnetic field levels were low; half of the subjects hadmean levels of </p></li><li><p>Magnetic Fields, Light-at-Night, and Melatonin 595</p><p>Am J Epidemiol Vol. 154, No. 7, 2001</p><p>in the model (listed in table 5). Participant age was signifi-cantly inversely associated with urinary 6-sulfatoxymela-tonin concentration: each additional year in age was associ-ated with approximately a 1 percent lower nocturnal urinary6-sulfatoxymelatonin level. Adding a quadratic term for agedid not materially alter the relation. Number of hours ofdarkness was directly associated with nocturnal 6-sulfa-toxymelatonin level: each additional hour of darkness wasassociated with a 2 percent higher 6-sulfatoxymelatoninconcentration. In none of the models was menopausal statusassociated with 6-sulfatoxymelatonin.</p><p>Relative to the lowest BMI category, each higher categorywas associated with approximately an 8 percent lower noc-turnal 6-sulfatoxymelatonin concentration. Reported use ofbeta blockers, calcium channel blockers, or psychotropicmedications was associated with approximately a 28 percentlower nocturnal urinary 6-sulfatoxymelatonin concentra-tion. Consumption of alcohol in the 24 hours precedingmorning urine collection was consistently related to a lower6-sulfatoxymelatonin concentration, but at suggestive levelsof significance (this relation is explored further in reference(25)). The following factors were not significantly associatedwith 6-sulfatoxymelatonin levels in any of the analyses andthus were excluded from subsequent models: current orrecent use of an electric blank...</p></li></ul>


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