Nightshift work, chronotype, and genome-wide DNA methylation in blood.

Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.e., measure of preference for activity earlier or later in the day) on DNA methylation among 110 of the female nightshift workers and an additional group of 131 male nightshift workers. Methylation data were generated using the Illumina Infinium HumanMethylation450 BeadChip (450K) Array. After applying the latest methylation data processing methods, we compared methylation levels at 361,210 CpG loci between the groups using linear regression models adjusted for potential confounders and applied the false-discovery rate (FDR) ≤ 0.05 to account for multiple comparisons. No statistically significant associations at the genome-wide level were observed with shift work or chronotype, though based on raw P values and absolute effect sizes, there were suggestive associations in genes that have been previously linked with cancer (e.g., BACH2, JRK, RPS6KA2) and type-2 diabetes (e.g., KCNQ1). Given that our study was underpowered to detect moderate effects, examining these suggestive results in well-powered independent studies or in pooled data sets may improve our understanding of the pathways underlying the negative health effects of shift work and the influence of personal factors such as chronotype. Such an approach may help identify potential interventions that can be used to protect the long-term health of shift workers.

Oxidative DNA damage during night shift work.

OBJECTIVES: We previously reported that compared with night sleep, day sleep among shift workers was associated with reduced urinary excretion of 8-hydroxydeoxyguanosine (8-OH-dG), potentially reflecting a reduced ability to repair 8-OH-dG lesions in DNA. We identified the absence of melatonin during day sleep as the likely causative factor. We now investigate whether night work is also associated with reduced urinary excretion of 8-OH-dG. METHODS: For this cross-sectional study, 50 shift workers with the largest negative differences in night work versus night sleep circulating melatonin levels (measured as 6-sulfatoxymelatonin in urine) were selected from among the 223 shift workers included in our previous study. 8-OH-dG concentrations were measured in stored urine samples using high performance liquid chromatography with electrochemical detection. Mixed effects models were used to compare night work versus night sleep 8-OH-dG levels. RESULTS: Circulating melatonin levels during night work (mean=17.1 ng/mg creatinine/mg creatinine) were much lower than during night sleep (mean=51.7 ng/mg creatinine). In adjusted analyses, average urinary 8-OH-dG levels during the night work period were only 20% of those observed during the night sleep period (95% CI 10% to 30%; p<0.001). CONCLUSIONS: This study suggests that night work, relative to night sleep, is associated with reduced repair of 8-OH-dG lesions in DNA and that the effect is likely driven by melatonin suppression occurring during night work relative to night sleep. If confirmed, future studies should evaluate melatonin supplementation as a means to restore oxidative DNA damage repair capacity among shift workers.

Oxidative DNA damage during sleep periods among nightshift workers.

OBJECTIVES: Oxidative DNA damage may be increased among nightshift workers because of suppression of melatonin, a cellular antioxidant, and/or inflammation related to sleep disruption. However, oxidative DNA damage has received limited attention in previous studies of nightshift work. METHODS: From two previous cross-sectional studies, urine samples collected during a night sleep period for 217 dayshift workers and during day and night sleep (on their first day off) periods for 223 nightshift workers were assayed for 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, using high-performance liquid chromatography with electrochemical detection. Urinary measures of 6-sulfatoxymelatonin (aMT6s), a marker of circulating melatonin levels, and actigraphy-based sleep quality data were also available. RESULTS: Nightshift workers during their day sleep periods excreted 83% (p=0.2) and 77% (p=0.03) of the 8-OH-dG that dayshift workers and they themselves, respectively, excreted during their night sleep periods. Among nightshift workers, higher aMT6s levels were associated with higher urinary 8-OH-dG levels, and an inverse U-shaped trend was observed between 8-OH-dG levels and sleep efficiency and sleep duration. CONCLUSIONS: Reduced excretion of 8-OH-dG among nightshift workers during day sleep may reflect reduced functioning of DNA repair machinery, which could potentially lead to increased cellular levels of oxidative DNA damage. Melatonin disruption among nightshift workers may be responsible for the observed effect, as melatonin is known to enhance repair of oxidative DNA damage. Quality of sleep may similarly impact DNA repair. Cellular levels of DNA damage will need to be evaluated in future studies to help interpret these findings.

Tumor marker usage and medical care costs among older early-stage breast cancer survivors.

PURPOSE: Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. METHODS: By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. RESULTS: We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. CONCLUSION: Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed.

Survival and lifetime costs associated with first-line bevacizumab use in older patients with metastatic colorectal cancer.

INTRODUCTION: The objective of this study was to investigate clinical effectiveness and incremental lifetime costs associated with first-line bevacizumab in older patients with metastatic colorectal cancer (mCRC). METHODS: Patients diagnosed with mCRC in 2004-2007 were identified from the Surveillance, Epidemiology, and End Results-Medicare database and stratified by first-line treatment (no chemotherapy [CTx], CTx alone, CTx plus bevacizumab). The impact of first-line bevacizumab on survival was investigated using a propensity score adjusted multivariate Cox proportional hazards model. Mean lifetime costs for each cohort were calculated using Medicare claims for all services rendered between diagnosis and end of follow-up, adjusting for death and censoring. RESULTS: A total of 4,414 patients (mean age: 77.3 years) were identified, of whom 15% received first-line bevacizumab. Among first-line-treated patients, bevacizumab receipt was associated with improved overall survival (hazard ratio: 0.85 [95% confidence interval: 0.75-0.97]; p = .013), and this benefit was limited to patients who received >1 month of bevacizumab therapy. Median and mean survival were greatest in patients treated with CTx plus bevacizumab relative to CTx alone (CTx plus bevacizumab median 19.4 months [mean 28.0 months] vs. CTx alone median 15.1 months [mean 22.9 months]; p < .001), as were mean lifetime costs (mean per patient cost $143,284 vs. $111,280). Compared with CTx alone, CTx plus bevacizumab was associated with a 5.1-month increase in mean survival and a $32,004 increase in mean lifetime treatment costs, with an incremental cost of $75,303 per life-year gained. CONCLUSION: Bevacizumab use is associated with longer survival than CTx alone in older patients treated in real-world clinical settings, at an incremental cost of $75,303 per life-year gained.

Cytokines in serum in relation to future non-Hodgkin lymphoma risk: evidence for associations by histologic subtype.

Specific associations for lymphoma in the general population suggest that chronic immune dysfunction/dysregulation may be associated with the development of B-cell non-Hodgkin lymphoma (NHL). Furthermore, polymorphisms in several cytokine genes have been associated with increased lymphoma risk, most consistently with genes for TNF and IL10. To evaluate the hypothesis that prediagnostic circulating cytokine levels would be associated with increased B-cell lymphoma risk, we conducted a nested case-control study within the Women's Health Initiative Observational Study cohort involving 491 B-cell NHL cases and 491 controls. Levels of eleven cytokines, including IL1ß, IL2, IL4, IL5, IL6, IL10, IL12, IL13, TNF, IFNγ and GM-CSF, were measured using a Luminex suspension bead-based multiplexed array in prediagnostic serum samples collected a median of 6 years prior to the lymphoma diagnosis. We observed a modestly increased risk of all B-cell NHL in women with increased levels of the cytokines TNF and IL10 (OR1.22, CI 1.07-1.38 and OR 1.09, CI 1.04-1.15, respectively, per doubling in the serum cytokine concentration) and this association showed some variation according to histologic subtype. The increased risk was strongest for those neoplasms diagnosed in close proximity to the blood draw for some histologic subtypes but not others, suggesting a component of reverse causation. Further study will be required to better understand how genetic polymorphisms in TNF and IL10 genes may interact with circulating cytokine levels and states of chronic immune dysfunction/stimulation to contribute to the risk of B-cell NHL.

The impact of chronotype on melatonin levels among shift workers.

OBJECTIVES: The association between shift work and cancer, which is thought to be mediated by effects on circulating melatonin levels, may be modified by chronotype (ie, the inherent preference for activity in the morning or the evening); however, few studies have examined the potential impact of chronotype on the carcinogenic effects of shift work. The authors analysed the impact of chronotype on previously reported differences in melatonin levels among healthcare workers that exclusively worked night or day shifts. METHODS: The cross-sectional study included 664 men and women (310 day shift and 354 night shift workers) from which urine samples were collected throughout work and sleep periods and were assayed for 6-sulfatoxymelatonin. Participants also completed the Composite Scale of Morningness, a questionnaire used to assess chronotype. RESULTS: Among both morning and evening-type night shift workers, 6-sulfatoxymelatonin levels were constitutively lower during daytime sleep, night-time sleep and night work compared with day shift workers during night-time sleep. However, morning-type night shift workers consistently showed 6-sulfatoxymelatonin levels that were closer to levels in day shift workers than did evening-type night shift workers. Differences in 6-sulfatoxymelatonin levels between morning-type and evening-type night shift workers relative to day shift workers were statistically significant in every instance (p<0.05). CONCLUSIONS: These results suggest that morning-type night shift workers may be better able to maintain a 'normal' circadian pattern of melatonin production as compared with evening-type night shift workers. The impact of this chronotype effect on cancer risk among shift workers requires further study.

Investigation of epstein-barr virus as a potential cause of B-cell non-Hodgkin lymphoma in a prospective cohort.

BACKGROUND: We hypothesized that poor control of Epstein-Barr virus (EBV) infection, leading to reactivation of the virus, increases the risk of non-Hodgkin lymphoma (NHL) in the general population of primarily immunocompetent persons. METHODS: We conducted a case-control study nested within the Women's Health Initiative Observational Study cohort in which we measured antibodies to EBV antigens [immunoglobulin G (IgG) to viral capsid antigen (VCA), nuclear antigen (EBNA1), and early antigen-diffuse (EA-D)] and EBV DNA load in prediagnostic samples of 491 B-cell NHL cases and 491 controls. RESULTS: We found no association with established EBV infection, based on seropositivity for VCA. Seropositivity for EBNA1 was associated with decreased risk of B-cell NHL, overall [OR = 0.5; 95% confidence interval (CI), 0.3-0.8] and for each of the histologic subtypes examined. Increased risk of chronic lymphocytic leukemia (CLL) and related subtypes was observed with higher levels of EBV DNA and antibody to EA-D, both markers reflective of reactivation. These associations were strongest for cases with the shortest time interval between blood draw and diagnosis. CONCLUSIONS: In balance, these results do not provide strong evidence of EBV playing a causal role in B-cell NHL in general population women. The associations we observed may reflect increased risk of NHL with underlying immune impairment or could be due to reverse causation. IMPACT: Further characterization of the subtype-specific association with CLL is warranted. Exclusion of cases with preclinical disease markers (such as monoclonal B-lymphocytosis for CLL) may help rule out reverse causation in future studies.

Night shift work and levels of 6-sulfatoxymelatonin and cortisol in men.

BACKGROUND: Night shift work is associated with cancer among men, but the biologic mechanism is unclear. We investigated whether male night shift workers showed changes in levels of melatonin and cortisol, potential biomarkers of cancer risk. METHODS: Urine was collected from 185 night shift and 158 day shift-working male healthcare providers, aged 22 to 55 years, throughout work and sleep periods, and assayed for 6-sulfatoxymelatonin and cortisol. Morning serum was collected within 90 minutes of completing the night and assayed for cortisol. RESULTS: Night shift workers had significantly lower 6-sulfatoxymelatonin levels during daytime sleep, nighttime work, and nighttime sleep on off-nights (57%, 62%, and 40% lower, respectively), relative to the day shift workers during nighttime sleep (P < 0.0001); urinary cortisol in night shift workers was 16% higher during daytime sleep and 13% lower during nighttime sleep on off-nights (P < 0.05). Morning serum cortisol post-work and post-sleep in night shift workers were 24% and 43% lower, respectively, than post-sleep levels among day shift workers (P < 0.0001). Within-subject comparisons among the night shift workers revealed significantly lower melatonin levels and significantly higher urinary cortisol levels during daytime sleep and nighttime work, relative to nighttime sleep (P < 0.01); morning serum cortisol levels post-work were lower than those post-sleep. CONCLUSIONS: Night shift workers have substantially lower 6-sulfatoxymelatonin during night work and daytime sleep, and levels remain low when night shift workers sleep at night. Chronic reduction in melatonin among night shift workers may be an important carcinogenic mechanism. Cortisol secretion patterns may be impacted by night shift work, which could affect cancer risk. IMPACT: Shift work could be an important risk factor for many types of cancer.

Racial differences in the association between night shift work and melatonin levels among women.

Reduced suppression of melatonin in response to working the night shift among people of Asian ancestry has been suggested as a possible explanation for the null results observed in a recent analysis of shift work and breast cancer risk in a Chinese cohort. The authors analyzed the impact of Asian versus white race on previously reported differences in urinary 6-sulfatoxymelatonin levels in a 2003-2008 study in Seattle, Washington, of female health-care workers that exclusively worked night or day shifts. A total of 225 white and 51 Asian participants were included in the analysis. Although 6-sulfatoxymelatonin levels were affected by night shift work in both racial groups, Asian night shift workers consistently showed 6-sulfatoxymelatonin levels that were closer to levels in day shift workers than did white night shift workers. Furthermore, differences in 6-sulfatoxymelatonin levels between white and Asian night shift workers relative to day shift workers were statistically significant in every instance (P < 0.05). These results suggest that Asians may be better able to maintain a "normal" circadian pattern of melatonin production compared with whites and suggest a biological mechanism by which Asian night shift workers may be at a reduced risk of cancer.

Invited commentary: Shift work and cancer.

In this issue of the Journal, Parent et al. (Am J Epidemiol. 2012;176(9):751-759) report significant associations between night-shift work and risk of cancer at several sites among men. These findings not only address the need for shift-work studies that evaluate cancers other than breast and prostate cancer but also support the increasing concern that the negative effects of shift work may be broadly applicable to risk of many cancers via the direct oncostatic properties of melatonin. Studies of shift work have been limited by a lack of detailed data for determining which aspects of this multifaceted exposure may be associated with increased cancer risk. Additionally, the influence of individual-level characteristics, such as preference for daytime activity versus nighttime activity or chronotype, has not been considered. In moving forward, launching new cohort studies of shift work and cancer risk is the most tenable approach, though it will be limited by the years of follow-up required in order to accrue adequate numbers of cancer cases. Studies incorporating biomarkers of effect are useful for providing immediate information that can aid not only in identifying the underlying mechanisms of the shift-work-cancer association but also in interpreting existing epidemiologic data and informing the design of future epidemiologic studies of cancer risk.

Markers of B-cell activation in relation to risk of non-Hodgkin lymphoma.

B-cell activation biomarkers have been associated with increased risk of non-Hodgkin lymphoma (NHL) in HIV-infected populations. However, whether a similar association may exist in general populations has not been established. We conducted a case-control study within the Women's Health Initiative Observational Study cohort to measure the B-cell activation biomarkers sCD23, sCD27, sCD30, sCD44, and CXCL13 in serum samples collected an average of 6 years before NHL diagnosis in 491 cases and 491 controls. Using logistic regression to estimate odds ratios, we observed strong associations between NHL and markers for all B-cell NHL and for major subtypes. Women with marker levels in the highest-versus-lowest quartile categories of CD23, CD27, CD30, or CXCL13 were at 2.8- to 5.5-fold increased risk of B-NHL. In addition, there were significant trends of risk with increasing levels of these markers present. Associations were strongest for cases with shortest lag times between blood draw and diagnosis (<3 years). However, there were also significant associations for cases with the longest prediagnostic lag (9 to 13 years). Taken together, our findings indicate a prominent role for B-cell activation among postmenopausal women in the etiology of B-cell NHL and/or in processes reflective of early disease development as early as 9 years before diagnosis.

Night shift work and hormone levels in women.

BACKGROUND: Night shift work may disrupt the normal nocturnal rise in melatonin, resulting in increased breast cancer risk, possibly through increased reproductive hormone levels. We investigated whether night shift work is associated with decreased levels of urinary 6-sulfatoxymelatonin, the primary metabolite of melatonin, and increased urinary reproductive hormone levels. METHODS: Participants were 172 night shift and 151 day shift-working nurses, aged 20-49 years, with regular menstrual cycles. Urine samples were collected throughout work and sleep periods and assayed for 6-sulfatoxymelatonin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrone conjugate (E1C). RESULTS: 6-Sulfatoxymelatonin levels were 62% lower and FSH and LH were 62% and 58% higher, respectively, in night shift-working women during daytime sleep than in day shift-working women during nighttime sleep (P ≤ 0.0001). Nighttime sleep on off-nights was associated with 42% lower 6-sulfatoxymelatonin levels among the night shift workers, relative to the day shift workers (P < 0.0001); no significant differences in LH or FSH were observed. 6-Sulfatoxymelatonin levels during night work were approximately 69% lower and FSH and LH were 35% and 38% higher, compared with day shift workers during nighttime sleep. No differences in E1C levels between night and day shift workers were observed. Within night shift workers, 6-sulfatoxymelatonin levels were lower and reproductive hormone levels were higher during daytime sleep and nighttime work, relative to nighttime sleep (P < 0.05). CONCLUSIONS: These results indicate that night shift workers have substantially reduced 6-sulfatoxymelatonin levels during night work and daytime sleep and that levels remain low even when a night shift worker sleeps at night. IMPACT: Shift work could be an important risk factor for many other cancers in addition to breast cancer.

Melatonin as a biomarker of circadian dysregulation.

It would be most useful to identify a biomarker of circadian dysregulation that could be used in epidemiologic studies of the effects of circadian disruption in humans. An indicator of circulating melatonin level has been shown to be a good biomarker of circadian dysregulation and has been associated with nightshift work and exposure to light-at-night in both laboratory-based and field studies. Among other circadian markers (such as core body temperature), it remains comparatively robust in the presence of various external influences. It can be reliably measured directly and indirectly through its metabolites in urine, blood, and saliva. Urinary melatonin has been shown to be stable over time, making it useful in epidemiologic studies in which laboratory processing is not immediately available, as well as studies of cancer with long latency periods. Several studies have shown melatonin to be useful in measuring diurnal type, which is of increasing interest as it becomes more apparent that successful adaptation to shift work may be dependent on diurnal preference.

Medication use and the risk of breast cancer.

PURPOSE: To investigate whether the use of commonly-prescribed medications, primarily antihypertensives and antidepressants, is associated with an increased risk of breast cancer. METHODS: Participants from a population-based case-control study were re-contacted 5-8 years after the original study regarding prescription and non-prescription medication use during the 10 years prior to diagnosis. Controls (n = 647) were frequency-matched to the cases (n = 600) by 5-year age groups. Medication use information was obtained during a telephone interview, and participants were sent the questionnaire in advance to facilitate recall. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression. RESULTS: A slightly increased risk of breast cancer was associated with use of calcium channel blockers (CCBs), but there was no trend with increasing duration or recency of use. Breast cancer risk was not associated with use of antidepressants, beta blockers, corticosteroids, or non-steroidal anti-inflammatory drugs. Results were similar when analyses were restricted to cases with localized disease. CONCLUSIONS: These results support previous findings that CCBs may be associated with modest increases in breast cancer risk, but not findings that non-steroidal anti-inflammatory use reduces risk.

Residential magnetic fields, medication use, and the risk of breast cancer.

BACKGROUND: Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing the nocturnal production of melatonin. The use of medications associated with reduced melatonin levels could modify this relationship. METHODS: We recontacted participants in a population-based case-control study of residential magnetic field exposure and breast cancer risk and interviewed them regarding medication use during the 10 years before diagnosis. Cases were diagnosed between November 1992 and March 1995, and magnetic field levels were measured in the home at diagnosis. We obtained medication use information by telephone interview from 558 cases and 588 controls. RESULTS: Breast cancer risk was not associated with exposure to residential magnetic fields, regardless of medication use. CONCLUSIONS: These results support previous findings that magnetic field exposure does not increase breast cancer risk.

Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle.

There is increasing interest in the possibility that disruption of normal circadian rhythm may increase the risk of developing cancer. Persons who engage in nightshift work may exhibit altered nighttime melatonin levels and reproductive hormone profiles that could increase the risk of hormone-related diseases, including breast cancer. Epidemiologic studies are now beginning to emerge suggesting that women who work at night, and who experience sleep deprivation, circadian disruption, and exposure to light-at-night are at an increased risk of breast cancer, and possibly colorectal cancer as well. Several studies have been conducted in Seattle recently to investigate the effects of factors that can disrupt circadian rhythm and alter normal nocturnal production of melatonin and reproductive hormones of relevance to breast cancer etiology. Studies completed to date have found: (1) an increased risk of breast cancer associated with indicators of exposure to light-at-night and night shift work; and (2) decreased nocturnal urinary levels of 6-sulphatoxymelatonin associated with exposure to 60-Hz magnetic fields in the bedroom the same night, and a number of other factors including hours of daylight, season, alcohol consumption and body mass index. Recently completed is an experimental crossover study designed to investigate whether exposure to a 60-Hz magnetic field under controlled conditions in the home sleeping environment is associated with a decrease in nocturnal urinary concentration of 6-sulphatoxymelatonin, and an increase in the urinary concentration of luteinizing hormone, follicle stimulating hormone, and estradiol in a sample of healthy women of reproductive age. Presently underway is a study to determine whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased urinary concentrations of the reproductive hormones listed above in a sample of healthy women of reproductive age, and to elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified. A proposal is under review to extend these studies to a sample of healthy men to investigate whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased concentrations of urinary cortisol and cortisone, urinary levels of a number of androgen metabolites, and serum concentrations of a number of reproductive hormones. Secondarily, the proposed study will elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified, as well as investigate whether polymorphisms of the genes thought to regulate the human circadian clock are associated with the ability to adapt to night shift work. It is anticipated that collectively these studies will enhance our understanding of the role of circadian disruption in the etiology of cancer.

Effects of 60-Hz magnetic field exposure on nocturnal 6-sulfatoxymelatonin, estrogens, luteinizing hormone, and follicle-stimulating hormone in healthy reproductive-age women: results of a crossover trial.

PURPOSE: Exposure to residential magnetic fields may disrupt the normal nocturnal rise in melatonin levels, resulting in increased risk for breast cancer, possibly through increased levels of reproductive hormones. We investigated whether exposure to a 60-Hz magnetic field under controlled conditions is associated with a decrease in urinary nocturnal 6-sulfatoxymelatonin level and increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen levels in healthy premenopausal women. METHODS: Using a crossover design, half the participants were assigned to magnetic field exposure of 5 to 10 mG greater than ambient levels for 5 consecutive nights during the early to midluteal phase of the menstrual cycle. On the last night of exposure, a nocturnal urine sample was collected. The next month, participants were sham exposed. The other half of participants were assigned the reverse order of exposure. RESULTS: Magnetic field exposure was associated with decreased 6-sulfatoxymelatonin levels, but no changes in reproductive hormone levels were observed. Participants using prescription medications and anovulatory participants had more pronounced decreases in 6-sulfatoxymelatonin levels with magnetic field exposure. CONCLUSION: This study provides further evidence that exposure to magnetic fields is associated with decreased nocturnal melatonin levels, but does not support the hypothesis that such exposure results in increased urinary levels of estrogens, LH, or FSH.

Soil ingestion in children and adults in the same family.

Ingestion of soil may be a potentially important pathway of exposure to environmental pollutants. Although several studies have estimated soil ingestion in children, data on ingestion in adults are sparse. The purposes of this study were to estimate soil ingestion in children aged 3 to 8 years and their parents, identify factors associated with increased ingestion, and compare ingestion rates within the same family. Food/liquid, excreta, and soil/dust samples were collected for the mother, father, and participant child for 11 consecutive days in 19 families. Soil ingestion was estimated using a mass balance approach. Soil ingestion levels in children were similar to those reported previously, whereas adult estimates were somewhat higher than previous estimates. Children's eating of dirt and parents' occupational contact with soil were associated with increased ingestion. Within families, soil ingestion levels in children and adults were not correlated, although this analysis was based on fewer than 19 participant families. Children's mean soil ingestion rates ranged from 37 to 207 mg/day depending on the tracer, with the highest values based on titanium as a tracer. Adult mean soil ingestion rates ranged from 23 to 625 mg/day depending on the tracer, with the highest value based on titanium as a tracer. Soil ingestion rate estimates were more variable in adults than in children.