Perimenarchal air pollution exposure and menstrual disorders.

STUDY QUESTION: What is the association between perimenarchal exposure to total suspended particulate (TSP) in air, menstrual irregularity phenotypes and time to menstrual cycle regularity? SUMMARY ANSWER: Exposures to TSP during high school are associated with slightly increased odds of menstrual irregularity and longer time to regularity in high school and early adulthood. WHAT IS KNOWN ALREADY: The menstrual cycle is responsive to hormonal regulation. Particulate matter air pollution has demonstrated hormonal activity. However, it is not known if air pollution is associated with menstrual cycle regularity. STUDY DESIGN, SIZE, DURATION: Cross sectional study of 34 832 of the original 116 430 women (29.91%) enrolled in 1989 from the Nurses' Health Study II (NHSII). The follow-up rate for this analytic sample was 97.76% at the 1991 survey. PARTICIPANTS/MATERIALS, SETTING, METHODS: Annual averages of TSP were available for each year of high school attendance. We created three case definitions including high school menstrual irregularity and androgen excess. The time to menstrual cycle regularity was reported by participants as <1 year, 1-2 years, 3-4 years, 5 years or longer, or never on the baseline questionnaire. Odds ratios and 95% confidence intervals (CI) were calculated for 45 µg/m3 increases in TSP exposure, adjusted for risk factors for menstrual irregularity. MAIN RESULTS AND THE ROLE OF CHANCE: In multivariable adjusted models, we observed that for every 45 µg/m3 increase in average high school TSP there was an increased odds (95%CI) of 1.08 (1.03-1.14), 1.08 (1.02-1.15) and 1.10 (0.98-1.25) for moderate, persistent, and persistent with androgen excess irregularity phenotypes, respectively. TSP was also associated with a longer time to cycle regularity, with stronger results among women with older ages at menarche and those living in the Northeast or the West. LIMITATIONS, REASONS FOR CAUTION: The outcomes of menstrual regularity and time to cycle regularity were retrospectively assessed outcomes and may be susceptible to recall bias. There is also the potential for selection bias, as women had to live until 2011 to provide addresses. WIDER IMPLICATIONS OF THE FINDINGS: Temporal exposure to air pollution in the adolescent and early adulthood window may be especially important, given its association with phenotypes of menstrual irregularity. The data from this study agrees with existing literature regarding air pollution and reproductive tract diseases. STUDY FUNDING/COMPETING INTEREST(S): Shruthi Mahalingaiah: Reproductive Scientist Development Program HD000849, and a research grant from the Boston University Department of Obstetrics and Gynecology, Stacey Missmer: R01HD57210 from the National Institute of Child Health and Human Development and the Massachusetts Institute of Technology Center for Environmental Health Sciences Translational Pilot Project Program, R01CA50385 from the National Cancer Institute, Jaime Hart and Francine Laden: 5R01ES017017 from the National Institute for Environmental Health Sciences, Jaime Hart: P30 ES00002 from the National Institute for Environmental Health Sciences at the National Institute of Health, The Nurses' Health Study II is supported by infrastructure grant UM1CA176726 from the National Cancer Institute, NIH, U.S. Department of Health and Human Services The authors have no conflicts of interest to declare.

Exposure to particulate matter air pollution and risk of multiple sclerosis in two large cohorts of US nurses.

BACKGROUND: Air pollution is thought to raise the risk of neurological disease by promoting neuroinflammation, oxidative stress, glial activation and cerebrovascular damage. Multiple Sclerosis is a common auto-immune disorder, primarily affecting young women. We conducted, to a large prospective study of particulate matter (PM) exposure and multiple sclerosis (MS) risk in two prospective cohorts of women: the Nurses Health Study (NHS) and the Nurses Health Study II (NHS II). METHODS: Cumulative average exposure to different size fractions of PM up to the onset of MS was estimated using spatio-temporal models. We used multivariable Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of MS associated with each size fraction of PM independently. Participants were followed from 1998 through 2004 in NHS and from 1988 through 2007 for NHS II. We conducted additional sensitivity analyses stratified by smoking, region of the US, and age, as well as analyses restricted to women who did not move during the study. Analyses were adjusted for age, ancestry, smoking, body mass index at age 18, region, tract level population density, latitude at age 15, and UV index. RESULTS: We did not observe significant associations between air pollution and MS risk in our cohorts. Among women in the NHS II, the HRs comparing the top vs. bottom quintiles of PM was 1.11 (95% Confidence Intervals (CI): 0.74, 1.66), 1.04 (95% CI: 0.73, 1.50) and 1.09 (95% CI: 0.73, 1.62) for PM10 (≤10µm in diameter), PM2.5 (≤2.5µm in diameter), and PM2.5-10 (2.5 to 10µm in diameter) respectively, and tests for linear trends were not statistically significant. No association between exposure to PM and risk of MS was observed in the NHS. CONCLUSIONS: In this study, exposure to PM air pollution was not related to MS risk.

Adult air pollution exposure and risk of infertility in the Nurses' Health Study II.

STUDY QUESTION: Is there an association between air pollution exposures and incident infertility? SUMMARY ANSWER: Increased exposure to air pollution is associated with an increased incidence of infertility. WHAT IS KNOWN ALREADY: Exposures to air pollution have been associated with lower conception and fertility rates. However, the impact of pollution on infertility incidence is unknown. STUDY DESIGN, SIZE, DURATION: Prospective cohort study using data collected from 116 430 female nurses from September 1989 to December 2003 as part of the Nurses' Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertility was defined by report of attempted conception for ≥12 months without success. Participants were able to report if evaluation was sought and if so, offer multiple clinical indications for infertility. After exclusion, 36 294 members were included in the analysis. Proximity to major roadways and ambient exposures to particulate matter less than 10 microns (PM10), between 2.5 and 10 microns (PM2.5-10), and less than 2.5 microns (PM2.5) were determined for residential addresses for the 36 294 members between the years of 1993 and 2003. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable adjusted Cox proportional hazard models with time-varying covariates. MAIN RESULTS AND THE ROLE OF CHANCE: Over 213 416 person-years, there were 2508 incident reports of infertility. Results for overall infertility were inconsistent across exposure types. We observed a small increased risk for those living closer to compared to farther from a major road, multivariable adjusted HR = 1.11 (CI: 1.02-1.20). This was consistent for those reporting primary or secondary infertility. For women living closer to compared to farther from a major road, for primary infertility HR = 1.05 (CI: 0.94-1.17), while for secondary infertility HR = 1.21 (CI: 1.07-1.36). In addition, the HR for every 10 µg/m(3) increase in cumulative PM2.5-10 among women with primary infertility was 1.10 (CI: 0.96-1.27), and similarly was 1.10 (CI: 0.94-1.28) for those with secondary infertility. LIMITATIONS, REASONS FOR CAUTION: Within the 2 year window of infertility diagnosis, we do not have the exact date of diagnosis or the exact timing of the start of attempting conception. As infertility status and subtypes of infertility were prospectively collected biennially, we were unable to tightly examine the timing of exposures on incidence of infertility. In terms of exposure quantification, we used ambient air pollution exposures as a proxy for personal exposures, potentially leading to exposure misclassification. However, several studies suggest that ambient measurements are an acceptable surrogate for individual level exposures in most populations. WIDER IMPLICATIONS OF THE FINDINGS: We observed an association between all size fractions of PM exposure, as well as traffic-related air pollution, and incidence of infertility. Of note, the strongest association was observed between cumulative average exposures over the course of follow-up and the risk of infertility, suggesting that chronic exposures may be of greater importance than short-term exposures. STUDY FUNDING/COMPETING INTERESTS: The work for this paper was supported by the following: S.M.: Reproductive Scientist Development Program HD000849, and the Building Interdisciplinary Research Careers in Women's Health HD043444, the Boston University CTSI 1UL1TR001430, and a research grant from the Boston University Department of Obstetrics and Gynecology, S.A.M.: R01HD57210 from the National Institute of Child Health and Human Development and the Massachusetts Institute of Technology Center for Environmental Health Sciences Translational Pilot Project Program, R01CA50385 from the National Cancer Institute, J.E.H. and F.L.: 5R01ES017017 from the National Institute for Environmental Health Sciences, 5 P42 ES007381 from the National Institute of Environmental Health at the National Institute of Health. L.V.F.: T32HD060454 in reproductive, perinatal, and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Nurses' Health Study II is additionally supported by infrastructure grant UM1CA176726 from the National Cancer Institute, NIH, U.S. Department of Health and Human Services. The authors have no actual or potential competing financial interests to disclose.

Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women.

BACKGROUND: Solar ultraviolet (UV) exposure estimated based on residential history has been used as a sun exposure indicator in previous case-control and descriptive studies. However, the associations of cumulative UV exposure based on residential history with different skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), have not been evaluated simultaneously in prospective studies. METHODS: We conducted a cohort study among 108,578 women in the Nurses' Health Study (1976-2006) to evaluate the relative risks of skin cancers with cumulative UV flux based on residential history in adulthood. RESULTS: Risk of SCC and BCC was significantly lower for women in lower quintiles vs the highest quintile of cumulative UV flux (both P for trend <0.0001). The association between cumulative UV flux and risk of melanoma did not reach statistical significance. However, risk of melanoma appeared to be lower among women in lower quintiles vs the highest quintile of cumulative UV flux in lag analyses with 2-10 years between exposure and outcome. The multivariable-adjusted hazard ratios per 200 × 10(-4) Robertson-Berger units increase in cumulative UV flux were 0.979 (95% confidence interval (CI): 0.933, 1.028) for melanoma, 1.072 (95% CI: 1.041, 1.103) for SCC, and 1.043 (95% CI: 1.034, 1.052) for BCC. CONCLUSIONS: Associations with cumulative UV exposure in adulthood among women differed for melanoma, SCC, and BCC, suggesting a potential variable role of UV radiation in adulthood in the carcinogenesis of the three major skin cancers.

Persistent organochlorine pesticides in serum and risk of Parkinson disease.

BACKGROUND: Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD. METHODS: We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey, with serum samples collected during 1968-1972, and analyzed in 2005-2007 for organochlorine pesticides. Incident PD cases were identified through the Social Insurance Institution's nationwide registry and were confirmed by review of medical records (n = 101). Controls (n = 349) were matched for age, sex, municipality, and vital status. Adjusted odds ratios (ORs) of PD were estimated using logistic regression. RESULTS: Little association emerged with a summary score of the 5 organochlorine pesticides found at high levels, and only increasing dieldrin concentrations trended toward a higher risk of PD (OR per interquartile range [IQR] 1.28, 95% confidence interval [CI] 0.97-1.69, p = 0.08). Because of possible strong confounding by cigarette smoking among smokers, we ran additional analyses restricted to never smokers (n = 68 cases, 183 controls). In these analyses, increasing dieldrin concentrations were associated with increased odds of PD (OR per IQR 1.95, 95% CI 1.26-3.02, p = 0.003). None of the other organochlorine pesticides were associated with PD in these analyses. CONCLUSIONS: These results provide some support for an increased risk of Parkinson disease with exposure to dieldrin, but chance or exposure correlation with other less persistent pesticides could contribute to our findings.

Chronic obstructive pulmonary disease mortality in railroad workers.

BACKGROUND: There is little information describing the risk of non-malignant respiratory disease and occupational exposure to diesel exhaust. METHODS: US railroad workers have been exposed to diesel exhaust since diesel locomotives were introduced after World War II. In a retrospective cohort study we examined the association of chronic obstructive pulmonary disease (COPD) mortality with years of work in diesel-exposed jobs. To examine the possible confounding effects of smoking, multiple imputation was used to model smoking history. A Cox proportional hazards model was used to estimate an incidence rate ratio, adjusted for age, calendar year, and length of follow-up after leaving work (to reduce bias due to a healthy worker survivor effect). RESULTS: Workers in jobs with diesel exhaust exposure had an increased risk of COPD mortality relative to those in unexposed jobs. Workers hired after the introduction of diesel locomotives had a 2.5% increase in COPD mortality risk for each additional year of work in a diesel-exposed job. This risk was only slightly attenuated after adjustment for imputed smoking history. CONCLUSIONS: These results support an association between occupational exposure to diesel exhaust and COPD mortality.

Urinary naphthalene and phenanthrene as biomarkers of occupational exposure to polycyclic aromatic hydrocarbons.

OBJECTIVES: The study investigated the utility of unmetabolised naphthalene (Nap) and phenanthrene (Phe) in urine as surrogates for exposures to mixtures of polycyclic aromatic hydrocarbons (PAHs). METHODS: The report included workers exposed to diesel exhausts (low PAH exposure level, n = 39) as well as those exposed to emissions from asphalt (medium PAH exposure level, n = 26) and coke ovens (high PAH exposure level, n = 28). Levels of Nap and Phe were measured in urine from each subject using head space-solid phase microextraction and gas chromatography-mass spectrometry. Published levels of airborne Nap, Phe and other PAHs in the coke-producing and aluminium industries were also investigated. RESULTS: In post-shift urine, the highest estimated geometric mean concentrations of Nap and Phe were observed in coke-oven workers (Nap: 2490 ng/l; Phe: 975 ng/l), followed by asphalt workers (Nap: 71.5 ng/l; Phe: 54.3 ng/l), and by diesel-exposed workers (Nap: 17.7 ng/l; Phe: 3.60 ng/l). After subtracting logged background levels of Nap and Phe from the logged post-shift levels of these PAHs in urine, the resulting values (referred to as ln(adjNap) and ln(adjPhe), respectively) were significantly correlated in each group of workers (0.71 < or = Pearson r < or = 0.89), suggesting a common exposure source in each case. Surprisingly, multiple linear regression analysis of ln(adjNap) on ln(adjPhe) showed no significant effect of the source of exposure (coke ovens, asphalt and diesel exhaust) and further suggested that the ratio of urinary Nap/Phe (in natural scale) decreased with increasing exposure levels. These results were corroborated with published data for airborne Nap and Phe in the coke-producing and aluminium industries. The published air measurements also indicated that Nap and Phe levels were proportional to the levels of all combined PAHs in those industries. CONCLUSION: Levels of Nap and Phe in urine reflect airborne exposures to these compounds and are promising surrogates for occupational exposures to PAH mixtures.

Occupational exposure to volatile organic compounds and aldehydes in the U.S. trucking industry.

Diesel exhaust is a complex chemical mixture that has been linked to lung cancer mortality in a number of epidemiologic studies. However, the dose-response relationship remains largely undefined, and the specific components responsible for carcinogenicity have not been identified. Although previous focus has been on the particulate phase, diesel exhaust includes a vapor phase of numerous volatile organic compounds (VOCs) and aldehydes that are either known or suspected carcinogens, such as 1,3-butadiene, benzene, and formaldehyde. However, there are relatively few studies that quantify exposure to VOCs and aldehydes in diesel-heavy and other exhaust-related microenvironments. As part of a nationwide assessment of exposure to diesel exhaust in the trucking industry, we collected measurements of VOCs and aldehydes at 15 different U.S. trucking terminals and in city truck drivers (with 6 repeat site visits), observing average shift concentrations in truck cabs and at multiple background and work area locations within each terminal. In this paper, we characterize occupational exposure to 18 different VOCs and aldehydes, as well as relationships with particulate mass (elemental carbon in PM < 1 microm and PM2.5) across locations to determine source characteristics. Our results show that occupational exposure to VOCs and aldehydes varies significantly across the different sampling locations within each terminal, with significantly higher exposures noted in the work environments over background levels (p < 0.01). A structural equation model performed well in predicting terminal exposures to VOCs and aldehydes as a function of job, background levels, weather conditions, proximity to a major road, and geographic location (R2 = 0.2-0.4 work area; R2 = 0.5-0.9 background).

Driver exposure to combustion particles in the U.S. Trucking industry.

A large study of combustion particle exposures for drivers of diesel-powered trucks was conducted in collaboration with an epidemiologic study of lung cancer outcomes for workers in the trucking industry. Three components of diesel exhaust combustion particles (PM(2.5), elemental carbon, and organic carbon) were measured inside the driver cabs of diesel-powered trucks from 36 different trucking terminals across the United States between 2001 and 2005. In-cab particle exposures for drivers assigned to both short and long distance trips were observed, as well as information on the smoking status of the driver, truck characteristics such as age and model, and weather conditions during the sampling session. This article summarizes these findings and describes the relationship between exhaust particles and various determinants of exposure. The results suggest that in-cab particle exposures are positively related to smoking, ambient particle concentrations, truck age, and open windows, with other significant modifying factors such as weather. This study represents the largest and most comprehensive exposure assessment of drivers in the trucking industry, encompassing a 4-year period of observations on diesel and exhaust particle exposures nationwide. The results are relevant not only to the occupational group of truck drivers being examined but also to the general population that live, commute, or work within proximity to diesel-fueled traffic or trucking terminals.

Modeling particle exposure in U.S. trucking terminals.

Multi-tiered sampling approaches are common in environmental and occupational exposure assessment, where exposures for a given individual are often modeled based on simultaneous measurements taken at multiple indoor and outdoor sites. The monitoring data from such studies is hierarchical by design, imposing a complex covariance structure that must be accounted for in order to obtain unbiased estimates of exposure. Statistical methods such as structural equation modeling (SEM) represent a useful alternative to simple linear regression in these cases, providing simultaneous and unbiased predictions of each level of exposure based on a set of covariates specific to the exposure setting. We test the SEM approach using data from a large exposure assessment of diesel and combustion particles in the U.S.trucking industry. The exposure assessment includes data from 36 different trucking terminals across the United States sampled between 2001 and 2005, measuring PM2.5 and its elemental carbon (EC), organic carbon (OC) components, by personal monitoring, and sampling at two indoor work locations and an outdoor "background" location. Using the SEM method, we predict the following: (1) personal exposures as a function of work-related exposure and smoking status; (2) work-related exposure as a function of terminal characteristics, indoor ventilation, job location, and background exposure conditions; and (3) background exposure conditions as a function of weather, nearby source pollution, and other regional differences across terminal sites. The primary advantage of SEMs in this setting is the ability to simultaneously predict exposures at each of the sampling locations, while accounting for the complex covariance structure among the measurements and descriptive variables. The statistically significant results and high R2 values observed from the trucking industry application supports the broader use of this approach in exposure assessment modeling.

Rotating night shifts and risk of breast cancer in women participating in the nurses' health study.

BACKGROUND: Melatonin shows potential oncostatic action, and light exposure during night suppresses melatonin production. There is little information, however, about the direct effect of night work on the risk of cancer. We investigated the effect of night work in breast cancer. METHODS: We examined the relationship between breast cancer and working on rotating night shifts during 10 years of follow-up in 78 562 women from the Nurses' Health Study. Information was ascertained in 1988 about the total number of years during which the nurses had worked rotating night shifts with at least three nights per month. From June 1988 through May 1998, we documented 2441 incident breast cancer cases. Logistic regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for confounding variables and breast cancer risk factors. All statistical tests were two-sided. RESULTS: We observed a moderate increase in breast cancer risk among the women who worked 1-14 years or 15-29 years on rotating night shifts (multivariate adjusted RR = 1.08 [95% CI = 0.99 to 1.18] and RR = 1.08 [95% CI = 0.90 to 1.30], respectively). The risk was further increased among women who worked 30 or more years on the night shift (RR = 1.36; 95% CI = 1.04 to 1.78). The test for trend was statistically significant (P =.02). CONCLUSIONS: Women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shifts.

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies.

BACKGROUND: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. METHODS: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. RESULTS: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women. CONCLUSIONS: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States.

Plasma organochlorine levels and the risk of breast cancer: an extended follow-up in the Nurses' Health Study.

The environmental organochlorines 2,2-bis(p-chlorophenyl)1,1,1,trichloroethane (DDT) and polychlorinated biphenyls (PCBs) have been implicated as potential causes of female breast cancer. We continued follow-up of our 1997 case-control study nested in the Nurses' Health Study cohort, adding 143 postmenopausal cases and controls to the original 238 pairs, and examining specific PCB congeners for the first time. We measured plasma levels of 2,2-bis(p-chlorophenyl)ethylene (DDE), the major metabolite of DDT, and PCBs prospectively, comparing women who were diagnosed with breast cancer between 1 month and 4 years after blood collection with control women in whom breast cancer did not develop. Median concentrations of lipid-adjusted DDE, total PCBs, and PCB numbers 118, 138, 153 and 180, assessed individually, were similar among the cases and controls. The multivariate relative risk of breast cancer for women in the highest quintile of exposure as compared with women in the lowest quintile was 0.82 for DDE (95% confidence interval [CI]: 0.49-1.37) and 0.84 for total PCBs (95% CI: 0.47-1.52), 0.69 for PCB 118 (95% CI: 0.39-1.22), 0.87 for PCB 138 (95% CI: 0.50-1.50), 0.83 for PCB 153 (95% CI: 0.47-1.48), and 0.98 for PCB 180 (95% CI: 0.55-1.75). Sub-group analyses were also performed. Overall, our results do not support the hypothesis that exposure to DDT and PCBs increases the risk of breast cancer.

Association of fine particulate matter from different sources with daily mortality in six U.S. cities.

Previously we reported that fine particle mass (particulate matter [less than and equal to] 2.5 microm; PM(2.5)), which is primarily from combustion sources, but not coarse particle mass, which is primarily from crustal sources, was associated with daily mortality in six eastern U.S. cities (1). In this study, we used the elemental composition of size-fractionated particles to identify several distinct source-related fractions of fine particles and examined the association of these fractions with daily mortality in each of the six cities. Using specific rotation factor analysis for each city, we identified a silicon factor classified as soil and crustal material, a lead factor classified as motor vehicle exhaust, a selenium factor representing coal combustion, and up to two additional factors. We extracted daily counts of deaths from National Center for Health Statistics records and estimated city-specific associations of mortality with each source factor by Poisson regression, adjusting for time trends, weather, and the other source factors. Combined effect estimates were calculated as the inverse variance weighted mean of the city-specific estimates. In the combined analysis, a 10 microg/m(3) increase in PM(2.5) from mobile sources accounted for a 3.4% increase in daily mortality [95% confidence interval (CI), 1.7-5.2%], and the equivalent increase in fine particles from coal combustion sources accounted for a 1.1% increase [CI, 0.3-2.0%). PM(2.5) crustal particles were not associated with daily mortality. These results indicate that combustion particles in the fine fraction from mobile and coal combustion sources, but not fine crustal particles, are associated with increased mortality.

Electric blanket use and breast cancer in the Nurses' Health Study.

Electric and magnetic fields (EMFs) have been hypothesized to increase the risk of breast cancer, and electric blankets represent an important source of exposure to EMFs. The authors examined the relation between electric blanket use and invasive breast cancer in the Nurses' Health Study. On the biennial questionnaire in 1992, 87,497 women provided information on this exposure during three consecutive time periods. In a prospective analysis with 301,775 person-years of follow-up through 1996 (954 cases), the relative risk for any electric blanket use was not elevated (relative risk (RR) = 1.08, 95% confidence interval (CI): 0.95, 1.24) after controlling for breast cancer risk factors. There was a weak association between breast cancer and electric blanket use at least 16 years before diagnosis and long-term use in age-adjusted analyses but not in multivariate models. In a retrospective analysis of 1,318,683 person-years of follow-up (2,426 cases), the multivariate relative risk associated with use before disease follow-up began was null (RR = 1.05, 95% CI: 0.95, 1.16). Similar results were obtained in analyses stratified by menopause and restricted to estrogen receptor-positive breast cancers. While 95% confidence intervals for these estimates did not exclude small risks, overall, results did not support an association between breast cancer risk and exposure to EMFs from electric blankets.

Predictors of plasma concentrations of DDE and PCBs in a group of U.S. women.

We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal attributes such as age, serum cholesterol, region of residence, adiposity, lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age (p = 0.0003), and PCBs increased 0.08 ppb (p = 0.0001). DDE and PCBs increased 0.20 (p = 0.02) and 0.13 ppb (p = 0.001), respectively, per 10 mg/dl serum cholesterol. Women living in the western United States had higher levels of DDE (mean = 11.0 ppb; p = 0.003), and women in the Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; p = 0.0002) as compared to women from other parts of the country (mean DDE = 6.3; mean PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption of meat, fish, poultry, dairy products, vegetables, fruits, and grains. There was a positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest. Using data from the cases in the nested case-control study to assess the predictive ability of the models, we confirmed that the most reliable predictors of DDE were age and serum cholesterol, and the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast. The null results for the majority of the food variables suggest that specific dietary factors, other than fish, are not currently a substantial contributor to human exposure to DDE and PCBs.

Environmental risk factors and female breast cancer.

The increasing incidence of breast cancer in the United States and the international variation in risk have led to speculation that environmental risk factors are an important cause of breast cancer. We review the epidemiologic evidence on the breast cancer risk associated with ambient environmental exposures experienced passively by the US population, and discuss the difficulties associated with measurement of specific exposures in environmental studies. We review geographic variation of breast cancer rates in the United States, and exposure to organochlorines, ionizing and electromagnetic radiation, and passive smoking. Results are inconclusive but do not support a major role of environmental risk factors in the etiology of breast cancer.

Plasma organochlorine levels and the risk of breast cancer.

BACKGROUND: Exposure to "environmental estrogens" such as organochlorines in pesticides and industrial chemicals has been proposed as a cause of increasing rates of breast cancer. Several studies have reported higher blood levels of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) in patients with breast cancer than in controls. METHODS: We measured plasma levels of DDE and PCBs prospectively among 240 women who gave a blood sample in 1989 or 1990 and who were subsequently given a diagnosis of breast cancer before June 1, 1992. We compared these levels with those measured in matched control women in whom breast cancer did not develop. Data on DDE were available for 236 pairs, and data on PCBs were available for 230 pairs. RESULTS: The median level of DDE was lower among case patients than among controls (4.71 vs. 5.35 parts per billion, P=0.14), as was the median level of PCBs (4.49 vs. 4.68 parts per billion, P=0.72). The multivariate relative risk of breast cancer for women in the highest quintile of exposure as compared with women in the lowest quintile was 0.72 for DDE (95 percent confidence interval, 0.37 to 1.40) and 0.66 for PCBs (95 percent confidence interval, 0.32 to 1.37). Exposure to high levels of both DDE and PCBs was associated with a nonsignificantly lower risk of breast cancer (relative risk for women in the highest quintiles of both DDE and PCBs as compared with women in the lowest, 0.43; 95 percent confidence interval, 0.13 to 1.44). CONCLUSIONS: Our data do not support the hypothesis that exposure to DDT and PCBs increases the risk of breast cancer.

Geographic variation in breast cancer incidence rates in a cohort of U.S. women.

BACKGROUND: Breast cancer mortality and incidence rates vary by geographic region in the United States. Previous analytic studies have measured mortality, not incidence, and have used regional prevalences to control for geographic variation in risk factors rather than adjusting for risk factors measured at the level of the individual. We prospectively evaluated regional variation in breast cancer incidence rates in the Nurses' Health Study and assessed the influence of breast cancer risk factors measured at the individual level. METHODS: The Nurses' Health Study cohort was established in 1976 when 121700 female nurses aged 30-55 years living in 11 U.S. states were enrolled. These states represent all four regions of the continental United States. We identified 3603 incident cases of invasive breast cancer through 1992 (1794565 person-years of follow-up). We calculated relative risks (RRs) adjusted for age and for age and established risk factors (i.e., multivariate-adjusted analysis), comparing California, the Northeast, and the Midwest with the South. RESULTS: For premenopausal women, there was little evidence of regional variation in breast cancer incidence rates, either in age-adjusted or in multivariate-adjusted analyses. For postmenopausal women in California, age-adjusted risk was modestly elevated (RR = 1.24; 95% confidence interval [CI] = 1.05-1.47); after adjusting for age and for established risk factors, the excess rate in California was attenuated by 25% (RR = 1.18; 95% CI = 1.00-1.40). No excess of breast cancer incidence was observed for postmenopausal women in either the Northeast or the Midwest. CONCLUSIONS: Little regional variation in age-adjusted breast cancer incidence rates was observed, with the exception of a modest excess for postmenopausal women in California. Adjustment for differences in the distribution of established risk factors explained some of the excess risk in California.

Reduced aliquot size for a plasma organochlorine assay for use in epidemiological studies.

Because archived blood specimens are an important but limited resource for conducting epidemiological studies using biomarkers, it is important to develop analytical techniques that minimize the amount of sample needed. We modified an established 1.0-ml blood plasma organochlorine assay to use smaller volumes. We assessed its utility by comparing the accuracy and precision of measurements obtained with different-sized aliquots of spiked plasma from three pools of known concentration of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs; low, medium, and high). There was a modest sacrifice in accuracy using 0.5 as opposed to 1.0 ml. However, the within-batch coefficients of variation, a measure of laboratory error, were consistently low when 0.5-ml aliquots were used. For both DDE and PCB concentrations, this error was less than 5% for the medium and high pools [5-20 parts per billion (ng/ml)] and less than 9% for the low pool (< 1 part per billion). After determining that aliquots of 0.5 ml were sufficient, we performed a blinded quality control analysis of stored plasma. In this study, the within-subject variation was low for DDE and PCBs and substantially lower than the between-subject variation, suggesting that the assay would rank subjects with reasonable precision. Our results suggest that use of 0.5-ml as opposed to 1.0-ml aliquots should not compromise the power of a nested case-control study to detect differences between subjects and would thus save plasma for future research. For populations with very low levels of organochlorines, however, the larger volumes should still be used.