The association between oil spill cleanup-related total hydrocarbon exposure and diabetes.

BACKGROUND: Although evidence suggests relationships between some crude oil components and glycemic dysregulation, no studies have examined oil spill-related chemical exposures in relation to type 2 diabetes mellitus (DM) risk. This study examined the relationship between total hydrocarbon (THC) exposure among workers involved in the 2010 Deepwater Horizon (DWH) oil spill and risk of DM up to 6 years afterward. METHODS: Participants comprised 2660 oil-spill cleanup or response workers in the prospective GuLF Study who completed a clinical exam and had no self-reported DM diagnosis prior to the spill. Maximum THC exposure was estimated with a job-exposure matrix based on interview data and personal measurements taken during cleanup operations. We defined incident DM by self-reported physician diagnosis of DM, antidiabetic medication use, or a measured hemoglobin A1c value ≥ 6.5%. We used log binomial regression to estimate risk ratios (RRs) for DM across ordinal categories of THC exposure. The fully adjusted model controlled for age, sex, race/ethnicity, education, employment status, and health insurance status. We also stratified on clinical body mass index categories. RESULTS: We observed an exposure-response relationship between maximum daily ordinal THC exposure level and incident DM, especially among overweight participants. RRs among overweight participants were 0.99 (95% CI: 0.37, 2.69), 1.46 (95% CI: 0.54, 3.92), and 2.11 (95% CI: 0.78, 5.74) for exposure categories 0.30-0.99 ppm, 1.00-2.99 ppm, and ≥3.00 ppm, respectively (ptrend = 0.03). CONCLUSION: We observed suggestively increasing DM risk with increasing THC exposure level among overweight participants, but not among normal weight or obese participants.

A prospective study of type 2 diabetes, metformin use, and risk of breast cancer.

BACKGROUND: Type 2 diabetes (T2D) has been associated with increased breast cancer risk, but commonly prescribed antidiabetic medications such as metformin may reduce risk. Few studies have investigated T2D and medications together in relation to breast cancer. PATIENTS AND METHODS: Data came from 44 541 Sister Study participants aged 35 to 74 years at enrollment (2003-2009) who satisfied eligibility criteria, followed through 15 September 2017. Information on time-varying, self-reported, physician-diagnosed, prevalent and incident T2D, use of antidiabetic medications, and covariates was obtained from baseline and follow-up questionnaires. Incident breast cancers were confirmed with medical records. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. RESULTS: During follow-up (median, 8.6 years), 2678 breast cancers were diagnosed at least 1 year after enrollment. There were 3227 women (7.2%) with prevalent and 2389 (5.3%) with incident T2D, among whom 61% (n = 3386) were ever treated with metformin. There was no overall association between T2D and breast cancer risk (HR 0.99; 95% CI, 0.87-1.13). However, T2D was associated with increased risk of triple-negative breast cancer (HR 1.40; 95% CI, 0.90-2.16). Compared with not having T2D, T2D with metformin use was not associated with overall breast cancer risk (HR 0.98; 95% CI, 0.83-1.15), but it was associated with decreased risk of estrogen receptor (ER)-positive breast cancer (HR 0.86; 95% CI 0.70-1.05) and increased risk of ER-negative (HR 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR 1.74; 95% CI, 1.06-2.83). The inverse association with ER-positive cancer was stronger for longer duration (≥10 year) metformin use (HR 0.62; 95% CI, 0.38-1.01; P for trend = 0.09). Results were supported by sensitivity analyses. CONCLUSION: Our findings suggest that associations between T2D and breast cancer may differ by hormone receptor status and that associations between T2D and ER-positive breast cancer may be reduced by long-term metformin use.

Maternal age at birth and daughters' subsequent childlessness.

STUDY QUESTION: Does maternal age at a daughter's birth predict her subsequent probability of lifelong childlessness? SUMMARY ANSWER: In this study population, women born to older mothers were more likely to be childless. WHAT IS KNOWN ALREADY: Although maternal age at childbearing is increasing in many countries, there is limited evidence on whether being born to older parents may influence offspring fertility. STUDY DESIGN SIZE AND DURATION: This analysis included 43 135 women from the US-based Sister Study, a cohort study of 50 884 sisters of women with breast cancer recruited between 2003 and 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants had no breast cancer at baseline. Women were included in the analytic sample if they were born between 1930 and 1964 and were at least 44 years old at enrolment. Median age when reproductive history was last ascertained was 63.8 years. We estimated relative risks (RR) and 95% CI of lifelong childlessness as a function of maternal age at birth, using multivariable log-binomial models, including total number of siblings, birth order, socioeconomic indicators of the family of origin, race and birth cohort. We examined the association in different subgroups and in a sibling-matched analysis including 802 sister pairs discordant for childlessness. MAIN RESULTS AND ROLE OF CHANCE: Compared with women born to 20-24-year-old mothers, those born to mothers aged 25-29, 30-34 and ≥35 years were more likely to be childless [RR (95% CI): 1.21 (1.14-1.29), 1.30 (1.22-1.39) and 1.40 (1.31-1.50), respectively]. The association was consistent in strata defined by birth cohort, number of siblings, birth order, and participant's educational level, as well as within sister pairs. Overall, we found weak evidence for an independent contribution of paternal age at birth to the daughter's probability of childlessness. LIMITATIONS REASONS FOR CAUTION: All participants had at least one sister, and all information was self-reported. We had no knowledge of whether childlessness was intentional and found only a modest association between maternal age at birth and self-reported indicators of infertility. Still, the association with childlessness was highly consistent. WIDER IMPLICATIONS OF THE FINDING: Given the widespread tendency to delay childbearing, evaluating the influence of maternal age at birth on offspring fertility is a public health priority. STUDY FUNDING/COMPETING INTERESTS: This research was supported in part by the Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005). The authors report no conflict of interest.

An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort.

BACKGROUND/OBJECTIVES: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study. SUBJECTS/METHODS: The Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing. RESULTS: Four CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases. CONCLUSIONS: Our findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease.

Tubal ligation in relation to menopausal symptoms and breast cancer risk.

BACKGROUND: Local inflammation after tubal ligation may affect ovarian function and breast cancer risk. METHODS: We analysed tubal ligation, menopausal characteristics, and breast cancer risk in the Sister Study cohort (N=50,884 women). RESULTS: Tubal ligation was associated with hot flashes (hazard ratio (HR) 1.09; 95% confidence interval (CI): 1.06-1.12) but not menopausal age (HR 0.99; 95% CI: 0.96-1.02). Tubal ligation did not have an impact on breast cancer overall (HR 0.95; 95% CI: 0.85-1.06), but had a suggested inverse relation with oestrogen receptor+/progesterone receptor+ invasive tumours (HR 0.84; 95% CI: 0.70-1.01), possibly because of subsequent hysterectomy/bilateral oophorectomy. CONCLUSION: Tubal ligation does not influence overall breast cancer risk.

Employment and work schedule are related to telomere length in women.

OBJECTIVES: To examine the association of employment and work schedule with shorter DNA telomeres, a marker of cellular ageing and disease risk factor, and consider whether differences were related to health, behaviours and sociodemographic factors, or varied by stress levels or menopausal status. METHODS: This cross-sectional analysis of 608 women aged 35-74 in the Sister Study examined determinants of relative telomere length (rTL) measured by quantitative PCR in leucocyte DNA. Age-adjusted regression models estimated base pair (bp) rTL differences for current and lifetime schedule characteristics (ie, part-time, full-time or overtime hours; multiple jobs; irregular hours; shiftwork; work at night). Covariates included race, smoking, perceived stress, sleep, physical activity, health and menopausal status, education, marital status, live births, children under 18, measured body mass index and urinary stress hormones. RESULTS: Compared with non-employed women with moderate or substantial past work histories (n=190), those currently working full-time (n=247; median 40 h/week) had a shorter rTL, an age-adjusted difference of -329 bp (95% CI -110 to -548). Longer-duration full-time work was also associated with shorter rTL (age-adjusted difference of -472 bp, 95% CI -786 to -158 for 20+ vs 1-5 years). Findings were not explained by health and demographic covariates. However, rTL differences for working at least full-time were greater in women with higher stress and epinephrine levels. CONCLUSIONS: Current and long-term full-time work were associated with shorter rTL, with differences of similar magnitude to smoking and history of heart disease or diabetes. Longitudinal data with specific stress measures are needed to further evaluate the impact of work schedule on rTL.

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study.

OBJECTIVES: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Príbram region, Czech Republic. METHODS: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. RESULTS: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. CONCLUSIONS: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out.

Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study.

Although specific pesticides have been associated with wheeze in farmers, little is known about pesticides and asthma. Data from 19,704 male farmers in the Agricultural Health Study were used to evaluate lifetime use of 48 pesticides and prevalent adult-onset asthma, defined as doctor-diagnosed asthma after the age of 20 yrs. Asthma cases were categorised as allergic (n = 127) and nonallergic (n = 314) based on their history of eczema or hay fever. Polytomous logistic regression, controlling for age, state, smoking and body mass, was used to assess pesticide associations. High pesticide exposure events were associated with a doubling of both allergic and nonallergic asthma. For ever-use, 12 individual pesticides were associated with allergic asthma and four with nonallergic asthma. For allergic asthma, coumaphos (OR 2.34; 95% CI 1.49-3.70), heptachlor (OR 2.01; 95% CI 1.30-3.11), parathion (OR 2.05; 95% CI 1.21-3.46), 80/20 mix (carbon tetrachloride/carbon disulfide) (OR 2.15; 95% CI 1.23-3.76) and ethylene dibromide (OR 2.07; 95% CI 1.02-4.20) all showed ORs of >2.0 and significant exposure-response trends. For nonallergic asthma, DDT (dichlorodiphenyltrichloroethane) showed the strongest association (OR 1.41; 95% CI 1.09-1.84), but with little evidence of increasing asthma with increasing use. Current animal handling and farm activities did not confound these results. There was little evidence that allergy alone was driving these associations. In conclusion, pesticides may be an overlooked contributor to asthma risk among farmers.

Pesticide use and menstrual cycle characteristics among premenopausal women in the Agricultural Health Study.

Menstrual cycle characteristics may have implications for women's fecundability and risk of hormonally related diseases. Certain pesticides disrupt the estrous cycle in animals. The authors investigated the cross-sectional association between pesticide use and menstrual function among 3,103 women living on farms in Iowa and North Carolina. Women were aged 21-40 years, premenopausal, not pregnant or breastfeeding, and not taking oral contraceptives. At study enrollment (1993-1997), women completed two self-administered questionnaires on pesticide use and reproductive health. Exposures of interest were lifetime use of any pesticide and hormonally active pesticides. Menstrual cycle characteristics of interest included cycle length, missed periods, and intermenstrual bleeding. The authors used generalized estimating equations to assess the association between pesticide use and menstrual cycle characteristics, controlling for age, body mass index, and current smoking status. Women who used pesticides experienced longer menstrual cycles and increased odds of missed periods (odds ratio = 1.5, 95% confidence interval: 1.2, 1.9) compared with women who never used pesticides. Women who used probable hormonally active pesticides had a 60-100% increased odds of experiencing long cycles, missed periods, and intermenstrual bleeding compared with women who had never used pesticides. Associations remained after control for occupational physical activity.

Animal production and wheeze in the Agricultural Health Study: interactions with atopy, asthma, and smoking.

BACKGROUND: Exposure to animals, their feeds, and by-products contribute to respiratory symptoms among farmers. AIMS: To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers. METHODS: Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994-97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers. RESULTS: Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (OR(dairy) = 1.26; OR(eggs) = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OR(eggs) was 2.88 among past smokers but only 1.46 for never smokers. The OR(eggs) for current smokers of 0.80 might reflect self selection of exposure among smokers. CONCLUSIONS: Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure.

Cancer incidence after childhood nasopharyngeal radium irradiation: a follow-up study in Washington County, Maryland.

A population from a hearing clinic in Washington County, Maryland, in 1943-1960 was followed to assess the risk of developing neoplasms from radium treatment of the nasopharynx for adenoid hypertrophy. Of the 2,925 subjects who attended the clinic, 904 received radium treatment. A nonconcurrent prospective study compared the cancer incidence among the irradiated persons with that among persons with other treatments. Seven brain tumor cases (three malignant and four benign) were identified in the irradiated group versus none in the nonirradiated group (relative risk = 14.8, 95% confidence interval: 0.76, 286.3). A nonsignificant excess risk of thyroid cancer was detected in the irradiated group based on two cases in the exposed group and one case in the nonexposed group (relative risk = 4.2, 95% confidence interval: 0.38, 46.6). Decreased risks of breast cancer, female genital cancers, and prostate cancer were observed among the irradiated individuals, although these deficits were not statistically significant individually. The decreased risk of sex hormone-related cancers in the irradiated group suggests possible radiation damage to the pituitary, with consequent reduction in pituitary hormone output and alterations in sexual and other hormonal development in early life. This hypothesis needs further evaluation.

Reproducibility of reported farming activities and pesticide use among breast cancer cases and controls. A comparison of two modes of data collection.

PURPOSE: Farming is associated with exposure to many potential hazards including pesticides and other agents, but the quality of self-reported data on farm exposures has not been well studied. METHODS: The reproducibility of self-reported farming history was evaluated among women in a population-based, case-control study of breast cancer in North Carolina. Thirty cases and 31 controls were randomly re-interviewed by telephone an average of 13.8 months after the initial interview. The initial interview was based on a farm-by-farm questionnaire, while the repeat interview was based on a shorter ever/never questionnaire. Agreement was estimated using proportions in exact agreement, kappa (kappa), and intraclass correlation coefficients (ICC). RESULTS: In general, group prevalences and means were higher on re-interview. Kappa estimates ranged from 0.15 to 0.84 among cases, and 0.26 to 0.87 among controls, with most estimates falling between 0.5 and 0.8. Moderate to almost perfect agreement (kappa) was observed for questions on crop work (0.47-0.70), crop type (0.56-0.82), pesticide application to tobacco (0.77), and farm residence (0.84). ICC estimates for continuous variables showed fair to substantial agreement (0.30 to 0.69 among cases, 0.38 to 0.69 among controls). Older cases, less educated cases, cases who lived on more than one farm, and cases with longer time intervals between interviews gave lower total agreement than similar groups of controls. CONCLUSIONS: Agreement estimates in this study are similar to those for other types of exposure information typically collected in epidemiologic studies. Nevertheless, a farm-by-farm method of exposure assessment may be preferable to an ever/never determination.

Studying the epidemiology of attention-deficit hyperactivity disorder: screening method and pilot results.

OBJECTIVE: As part of a larger epidemiologic study of risk factors for attention-deficit hyperactivity disorder (ADHD), this pilot study combined parent and teacher information to estimate ADHD prevalence among elementary school children in a North Carolina county. The methods developed for this study and the pitfalls we encountered illustrate the challenges involved in conducting population-based studies of ADHD. METHODS: We employed 2-stage screening using DSM-IV criteria. Teachers completed behaviour-rating scales for all children. We then administered a structured telephone interview to parents of potential cases. We screened 362 of 424 (85%) children in grades 1 to 5 in 4 schools. RESULTS: According to parent reports, 43 children (12%) had previously been diagnosed with ADHD by a health professional. Thirty-four children (9%) were taking ADHD medication. Forty-six children (12.7%) met study case criteria for ADHD, based on combined teacher and parent reports. Of the 46 cases, 18 (39%) had not been previously identified. Eight previously diagnosed children, however, did not meet case criteria. After we adjusted for nonresponse, the estimated prevalence was 16% (95%CI, 12% to 20%). CONCLUSIONS: These data suggest that the DSM-IV prevalence of ADHD has been substantially underestimated, although the true prevalence in this population may be less than the 16% estimated here. Population-based studies of ADHD are feasible and may provide important information about practice and treatment patterns in community settings, as well as a broader understanding of the etiology and life course of this common disorder.

A population-based case-control study of farming and breast cancer in North Carolina.

We examined the role of farming and pesticide exposure among 862 cases and 790 controls in a population-based, case-control study of breast cancer conducted in North Carolina between 1993 and 1996. We obtained exposure information through personal interview. Increasing duration of farming was inversely associated with breast cancer risk; odds ratios (95% confidence intervals) were 1.2 (0.8-1.7), 0.8 (0.5-1.2), 0.7 (0.5-1.1), and 0.6 (0.4-0.9) for 1-10, 11-17, 18-23, and >23 years of farming, respectively, relative to nonfarmers. Inverse associations persisted when farming was restricted to calendar time periods of 2,2-bis(p-chlorophenyl)- 1,1,1-trichloroethane (DDT) use or to farming at ages 9-16. Among women who farmed, odds ratios (ORs) were elevated for those who reported being present in fields during or shortly after pesticide application (OR = 1.8, 95% CI = 1.1-2.8) and for those who reported not using protective clothing while applying pesticides (OR = 2.0; 95% CI = 1.0-4.3), but not among those who reported using protective clothing (OR = 0.8; 95% CI = 0.4-1.8). We conclude that residence or work on farms may be associated with a reduced risk of breast cancer. Nevertheless, our results suggest a possible increased risk of breast cancer among a subgroup of farming women who were most likely to be exposed to pesticides.

Risk of ovarian cancer in relation to use of phenolphthalein-containing laxatives.

We examined ovarian cancer risk in relation to use of phenolphthalein-containing laxatives in 410 epithelial ovarian cancer cases and 713 controls. Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of ovarian cancer (odds ratio, OR, 1.1, 95% confidence interval, CI, 0.9-1.4). Risk was slightly, but not significantly, higher with more frequent use (OR 1.2 for 75 or more days of use). When women who used non-phenolphthalein containing laxatives was used as the reference group, the associations were slightly, but not significantly larger (OR 1.4 for any use of phenolphthalein-containing laxatives and OR 1.5 for 75 or more days of use)

Dietary intake of calcium, magnesium and antioxidants in relation to risk of amyotrophic lateral sclerosis.

Dietary factors have long been suspected of being risk factors for amyotrophic lateral sclerosis (ALS), but few human studies have been reported. To address several of the dietary hypotheses, a case-control study of risk factors for ALS conducted in New England in 1993-1996 included an abbreviated food frequency questionnaire. We examined the dietary intake of calcium, magnesium and antioxidants among 107 ALS cases and 262 community controls. Overall, these dietary factors were not related to risk of ALS, though modestly protective associations were suggested for magnesium and lycopene.

A model for predicting the frequency of high pesticide exposure events in the Agricultural Health Study.

The frequency of self-reported high pesticide exposure events (HPEE) has been recorded in the NCI/EPA/NIEHS Agricultural Health Study (AHS). Fourteen percent (14%) of the enrolled applicators responding reported "an incident or experience while using any pesticide which caused an unusually high exposure." These data show, as expected, that the probability of a report of an HPEE increases with the cumulative number of days of pesticide application reported by the applicator. We have developed a three-parameter model that predicts the risk odds ratio (OR) of an HPEE as a function of the number of days that pesticides are applied. These events are costly in terms of resulting health-care visits, lost time from work, and potential risk for cancer and other chronic diseases. We propose that failure to carefully follow all the pesticide manufacturer's label requirements, inexperience, and random events (i.e., breaking hose) are the three factors responsible for the events observed. Special precautions for new or infrequent users of pesticides are indicated.

Indoor residential radon exposure and risk of childhood acute myeloid leukaemia.

Exposure to radon has been identified as a risk factor for lung cancer in uranium miners, but evidence of adverse health effects due to indoor radon exposure is inconsistent. Ecological studies have suggested a correlation between indoor radon levels and leukaemia incidence. We evaluated the risk associated with indoor residential radon exposure within a larger interview-based case-control study of risk factors for childhood acute myeloid leukaemia (AML). A total of 173 cases and 254 controls met the eligibility criteria, and information was collected through telephone interviews with parents and analysis of alpha-track radon detectors placed in the home for a period of 1 year. No association was observed between radon exposure and risk of AML, with adjusted odds ratios of 1.2 (95% confidence interval (CI) 0.7-1.8) for 37-100 Bq m(-3) and 1.1 (95% CI 0.6-2.0) for > 100 Bq m(-3) compared with < 37 Bq m(-3). Although there was an inverse association between radon level and AML risk among children < 2 years at diagnosis, among children > or = 2 years, AML risk was increased among those with higher radon exposure. The observed association after age 2 is most likely due to chance. Overall, there was no association between residential radon and risk of childhood AML.

Active and passive smoking and the occurrence of natural menopause.

We examined smoking in relation to natural menopause in 543 women who prospectively recorded menstrual data from their 20s. Mean age at natural menopause was 0.8 years younger (95% CL = -1.5, -0.0) in 98 women who smoked at menopause compared with 362 never-smokers (RR 1.3, 95% CI = 1.0-1.7). We did not observe a decrease in age at natural menopause in former smokers, a dose-response among current smokers, or a lower age at menopause with passive smoke exposure at home. These results suggest that the effect of smoking on ovarian senescence is limited to active smoking during the menopausal transition.