Publications by authors named "Dale P Sandler"

480 Publications

Using Real-Time Area VOC Measurements to Estimate Total Hydrocarbons Exposures to Workers Involved in the Deepwater Horizon Oil Spill.

Ann Work Expo Health 2021 Sep 13. Epub 2021 Sep 13.

Exposure Assessment Applications, LLC, 6045 N 27th Street, Arlington, VA 22207, USA.

Even though the Deepwater Horizon oil spill response and clean-up (OSRC) had one of the largest exposure monitoring efforts of any oil spill, a number of exposure groups did not have sufficient personal data available or there were gaps in days measured to adequately characterize exposures for the GuLF STUDY, an epidemiologic study investigating the health of the OSRC workers. Area measurements were available from real-time air monitoring instruments and used to supplement the personal exposure measurements.

Objectives: The objective was to present a method that used real-time volatile organic compounds (VOCs) area measurements transformed to daily total hydrocarbons (THC) time-weighted averages (TWAs) to supplement THC personal full-shift measurements collected using passive charcoal badges. A second objective was to develop exposure statistics using these data for workers on vessels piloting remotely operated vehicle (ROV) vessels and other marine vessels (MVs) not at the job title level, but at the vessel level.

Methods: From hourly vessel averages derived from ~26 million real-time VOC measurements, we estimated full-shift VOC TWAs. Then, we determined the relationship between these TWAs and corresponding full-shift THC personal measurements taken on the same vessel-day. We used this relationship to convert the full-shift VOC measurements to full-shift 'THC' TWA estimates when no personal THC measurements existed on a vessel-day. We then calculated arithmetic means (AMs) and other statistics of THC exposures for each vessel.

Results: The VOC-derived estimates substantially supplemented the THC personal measurements, with the number of vessel-days for which we have exposure estimates increasing by ~60%. The estimates of the AMs are some of the highest observed in the GuLF STUDY. As expected, the AMs decreased over time, consistent with our findings on other vessels.

Conclusions: Despite the inherent limitations of using real-time area measurements, we were able to develop additional daily observations of personal THC exposures for workers on the ROV vessels and other MVs over time. The estimates likely resulted in more representative estimates of the AMs in the GuLF STUDY. The method used here can be applied in other occupational settings and industries for personal exposure estimation where large amounts of area measurements and more limited numbers of personal measurements are available.
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http://dx.doi.org/10.1093/annweh/wxab066DOI Listing
September 2021

Linear Relationships Between Total Hydrocarbons and Benzene, Toluene, Ethylbenzene, Xylene, and n-Hexane during the Deepwater Horizon Response and Clean-up.

Ann Work Expo Health 2021 Sep 2. Epub 2021 Sep 2.

Exposure Assessment Applications, LLC, 6045 N. 27th. St., Arlington, VA 22207, USA.

Objectives: Our objectives were to (i) determine correlations between measurements of THC and of BTEX-H, (ii) apply these linear relationships to predict BTEX-H from measured THC, (iii) use these correlations as informative priors in Bayesian analyses to estimate exposures.

Methods: We used a Bayesian left-censored bivariate framework for all 3 objectives. First, we modeled the relationships (i.e. correlations) between THC and each BTEX-H chemical for various overarching groups of measurements using linear regression to determine if correlations derived from linear relationships differed by various exposure determinants. We then used the same linear regression relationships to predict (or impute) BTEX-H measurements from THC when only THC measurements were available. Finally, we used the same linear relationships as priors for the final exposure models that used real and predicted data to develop exposure estimate statistics for each individual exposure group.

Results: Correlations between measurements of THC and each of the BTEX-H chemicals (n = 120 for each of BTEX, 36 for n-hexane) differed substantially by area of the Gulf of Mexico and by time period that reflected different oil-spill related exposure opportunities. The correlations generally exceeded 0.5. Use of regression relationships to impute missing data resulted in the addition of >23 000 n-hexane and 541 observations for each of BTEX. The relationships were then used as priors for the calculation of exposure statistics while accounting for censored measurement data.

Conclusions: Taking advantage of observed relationships between THC and BTEX-H allowed us to develop robust exposure estimates where a large amount of data were missing, strengthening our exposure estimation process for the epidemiologic study.
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http://dx.doi.org/10.1093/annweh/wxab064DOI Listing
September 2021

Gestational diabetes and risk of breast cancer before age 55 years.

Int J Epidemiol 2021 Aug 29. Epub 2021 Aug 29.

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA.

Background: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting.

Methods: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors.

Results: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women.

Conclusions: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM.
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http://dx.doi.org/10.1093/ije/dyab165DOI Listing
August 2021

Exposure Assessment Techniques Applied to the Highly Censored Deepwater Horizon Gulf Oil Spill Personal Measurements.

Ann Work Expo Health 2021 Aug 21. Epub 2021 Aug 21.

Stewart Exposure Assessments, LLC, Arlington, VA, USA.

The GuLF Long-term Follow-up Study (GuLF STUDY) is investigating potential adverse health effects of workers involved in the Deepwater Horizon (DWH) oil spill response and cleanup (OSRC). Over 93% of the 160 000 personal air measurements taken on OSRC workers were below the limit of detection (LOD), as reported by the analytic labs. At this high level of censoring, our ability to develop exposure estimates was limited. The primary objective here was to reduce the number of measurements below the labs' reported LODs to reflect the analytic methods' true LODs, thereby facilitating the use of a relatively unbiased and precise Bayesian method to develop exposure estimates for study exposure groups (EGs). The estimates informed a job-exposure matrix to characterize exposure of study participants. A second objective was to develop descriptive statistics for relevant EGs that did not meet the Bayesian criteria of sample size ≥5 and censoring ≤80% to achieve the aforementioned level of bias and precision. One of the analytic labs recalculated the measurements using the analytic method's LOD; the second lab provided raw analytical data, allowing us to recalculate the data values that fell between the originally reported LOD and the analytical method's LOD. We developed rules for developing Bayesian estimates for EGs with >80% censoring. The remaining EGs were 100% censored. An order-based statistical method (OBSM) was developed to estimate exposures that considered the number of measurements, geometric standard deviation, and average LOD of the censored samples for N ≥ 20. For N < 20, substitution of ½ of the LOD was assigned. Recalculation of the measurements lowered overall censoring from 93.2 to 60.5% and of the THC measurements, from 83.1 to 11.2%. A total of 71% of the EGs met the ≤15% relative bias and <65% imprecision goal. Another 15% had censoring >80% but enough non-censored measurements to apply Bayesian methods. We used the OBSM for 3% of the estimates and the simple substitution method for 11%. The methods presented here substantially reduced the degree of censoring in the dataset and increased the number of EGs meeting our Bayesian method's desired performance goal. The OBSM allowed for a systematic and consistent approach impacting only the lowest of the exposure estimates. This approach should be considered when dealing with highly censored datasets.
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http://dx.doi.org/10.1093/annweh/wxab060DOI Listing
August 2021

Lung and extrathoracic cancer incidence among underground uranium miners exposed to radon progeny in the Příbram region of the Czech Republic: a case-cohort study.

Occup Environ Med 2021 Aug 20. Epub 2021 Aug 20.

Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.

Objectives: Radon is carcinogenic, but more studies are needed to understand relationships with lung cancer and extrathoracic cancers at low exposures. There are few studies evaluating associations with cancer incidence or assessing the modifying effects of smoking.

Methods: We conducted a case-cohort study with 16 434 underground uranium miners in the Czech Republic with cancer incidence follow-up 1977-1996. Associations between radon exposure and lung cancer, and extrathoracic cancer, were estimated with linear excess relative rate (ERR) models. We examined potential modifying effects of smoking, time since exposure and exposure rate.

Results: Under a simple ERR model, assuming a 5-year exposure lag, the estimated ERR of lung cancer per 100 working level months (WLM) was 0.54 (95% CI 0.33 to 0.83) and the estimated ERR of extrathoracic cancer per 100 WLM was 0.07 (95% CI -0.17 to 0.72). Most lung cancer cases were observed among smokers (82%), and the estimated ERR of lung cancer per 100 WLM was larger among smokers (ERR/100 WLM=1.35; 95% CI 0.84 to 2.15) than among never smokers (ERR/100 WLM=0.12; 95% CI -0.05 to 0.49). Among smokers, the estimated ERR of lung cancer per 100 WLM decreased with time since exposure from 3.07 (95% CI -0.04 to 10.32) in the period 5-14 years after exposure to 1.05 (95% CI 0.49 to 1.87) in the period 25+ years after exposure.

Conclusions: We observed positive associations between cumulative radon exposure and lung cancer, consistent with prior studies. We observed a positive association between cumulative radon exposure and extrathoracic cancers, although the estimates were small. There was evidence that the association between radon and lung cancer was modified by smoking in a multiplicative or super-multiplicative fashion.
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http://dx.doi.org/10.1136/oemed-2021-107392DOI Listing
August 2021

Ambient particulate matter, ozone, and neurologic symptoms in U.S. Gulf states adults.

Environ Epidemiol 2021 Aug 6;5(4):e160. Epub 2021 Aug 6.

Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina.

Research on neurologic effects of air pollution has focused on neurodevelopment or later-life neurodegeneration; other effects throughout adulthood have received less attention. We examined air pollution levels and neurologic symptoms among 21,467 adults in US Gulf Coast states. We assigned exposure using Environmental Protection Agency estimates of daily ambient particulate matter 2.5 (PM) and ozone. Gulf Long-term Follow-up Study participants reported neurologic symptoms at enrollment (2011-2013). We estimated cross-sectional associations between each air pollutant and prevalence of "any" neurologic, central nervous system (CNS), or peripheral nervous system (PNS) symptoms. Ambient PM was consistently associated with prevalence of neurologic symptoms. The highest quartile of 30-day PM was associated with any neurologic symptom (prevalence ratio [PR] = 1.16; 95% confidence interval [CI] = 1.09, 1.23) and there were increasing monotonic relationships between 30-day PM and each symptom category (-trend ≤ 0.01). Associations with PM were slightly stronger among nonsmokers and during colder seasons. The highest quartile of 7-day ozone was associated with increased prevalence of PNS symptoms (PR = 1.09; 95% CI = 1.00, 1.19; -trend = 0.03), but not with other outcomes. Ozone concentrations above regulatory levels were suggestively associated with neurologic symptoms (PR = 1.06; 95% CI = 0.99, 1.14). Mutual adjustment in co-pollutant models suggests that PM is more relevant than ozone in relation to prevalence of neurologic symptoms.
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http://dx.doi.org/10.1097/EE9.0000000000000160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367062PMC
August 2021

Blood DNA methylation profiles improve breast cancer prediction.

Mol Oncol 2021 Aug 19. Epub 2021 Aug 19.

Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, 27709, USA.

Although blood DNA methylation (DNAm) profiles are reported to be associated with breast cancer incidence, they have not been widely used in breast cancer risk assessment. Among a breast cancer case-cohort of 2,774 women (1,551 cases) in the Sister Study, we used candidate CpGs and DNAm estimators of physiologic characteristics to derive a methylation-based breast cancer risk score, mBCRS. Overall, 19 CpGs and five DNAm estimators were selected using elastic net regularization to comprise mBCRS. In a test-set, higher mBCRS was positively associated with breast cancer incidence, showing similar strength to the polygenic risk score (PRS) based on 313 single-nucleotide polymorphisms (313-SNP). Area under the curve (AUC) for breast cancer prediction was 0.60 for self-reported risk factors (RFs), 0.63 for PRS and 0.63 for mBCRS. Adding mBCRS to PRS and RFs improved breast cancer prediction from 0.66 to 0.71. mBCRS findings were replicated in a nested case-control study within the EPIC-Italy cohort. These results suggest that mBCRS, a risk score derived using blood DNAm, can be used to enhance breast cancer prediction.
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http://dx.doi.org/10.1002/1878-0261.13087DOI Listing
August 2021

Estimation of Airborne Vapor Concentrations of Oil Dispersants COREXIT™ EC9527A and EC9500A, Volatile Components Associated with the Deepwater Horizon Oil Spill Response and Clean-up Operations.

Ann Work Expo Health 2021 Aug 19. Epub 2021 Aug 19.

Stewart Exposure Assessments, LLC, 6045 N. 27th St., Arlington, VA 22207, USA.

The Deepwater Horizon (DWH) drilling unit explosion above the Macondo oil well on 20 April 2010 caused the release of approximately 4.9 million barrels (779 million L) of oil into the Gulf of Mexico. As part of a larger spill response and clean-up effort, approximately 1.84 million gallons (6.81 million L) of chemical dispersants COREXIT™ EC9500A and COREXIT™ EC9527A were applied to the resultant oil slicks through spraying on the water surface by plane and by vessel and through injection at the release source near the seabed. The GuLF STUDY is investigating the health effects of workers involved in the oil spill response and clean-up after the DWH explosion, and estimates of possible exposure to chemical dispersants were needed. Exposures were estimated to the volatile components of COREXIT™ EC9500A [petroleum distillates, hydrotreated light, and propylene glycol (PG)] and of COREXIT™ EC9527A [2-butoxyethanol (2-BE) and PG] using two of AIHA IHMOD2.0© mathematical modeling tools along with the dispersants' chemical and physical properties. Monte Carlo simulations were used to reflect uncertainty in input parameters with both the two-box, constant emission model and the near and mid field plume model for indoor and outdoor activities, respectively. Possible exposure scenarios considered various evaporation rates, sizes of the dispersant pool, wind speeds, and ventilation rates. For the two-box model, mean near field exposure estimates to 2-BE ranged from 0.9 to 5.7 ppm, while mean far field estimated exposures ranged from 0.3 to 3.5 ppm. Estimates of mean near field plume model exposures ranged from 0.01 to 3.7 ppm at 2.5 ft from the source, and <0.01 to 0.3 ppm at 10 ft from the source. Estimated exposures to PG were approximately 10% of the calculated 2-BE exposures and exposures to petroleum distillates about 40% higher than the 2-BE estimates. Results indicate that compared with current occupational exposure guidelines, overexposure to petroleum distillates and PG probably did not occur in our study, but under some conditions, for short periods, exposure to 2-BE may have exceeded the limits for peak exposures. These estimates were developed for use in job-exposure matrices to estimate exposures of workers having contact with dispersant vapors for the GuLF STUDY.
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http://dx.doi.org/10.1093/annweh/wxab056DOI Listing
August 2021

Estimates of Inhalation Exposures among Land Workers during the Deepwater Horizon Oil Spill Clean-up Operations.

Ann Work Expo Health 2021 Aug 9. Epub 2021 Aug 9.

Stewart Exposure Assessments, LLC, Arlington, VA, USA.

Following the Deepwater Horizon oil spill disaster, thousands of workers and volunteers cleaned the shoreline across four coastal states of the Gulf of Mexico. For the GuLF STUDY, we developed quantitative estimates of oil-related chemical exposures [total petroleum hydrocarbons (THC), benzene, toluene, ethylbenzene, xylene, and n-hexane (BTEX-H)] from personal measurements on workers performing various spill clean-up operations on land. These operations included decontamination of vessels, equipment, booms, and personnel; handling of oily booms; hazardous waste management; beach, marsh, and jetty clean-up; aerial missions; wildlife rescue and rehabilitation; and administrative support activities. Exposure estimates were developed for unique groups of workers by (i) activity, (ii) state, and (iii) time period. Estimates of the arithmetic means (AMs) for THC ranged from 0.04 to 3.67 ppm. BTEX-H estimates were substantially lower than THC (in the parts per billion range). Both THC and BTEX-H estimates were substantially lower than their respective occupational exposure limits. The work group, 'Fueled engines' consistently was one of the higher exposed groups to THC and BTEX-H. Notable differences in the AM exposures were observed by activity, time and, to a lesser degree, by state. These exposure estimates were used to develop job-exposure matrices for the GuLF STUDY.
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http://dx.doi.org/10.1093/annweh/wxab028DOI Listing
August 2021

Genetic insights into biological mechanisms governing human ovarian ageing.

Nature 2021 08 4;596(7872):393-397. Epub 2021 Aug 4.

Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.

Reproductive longevity is essential for fertility and influences healthy ageing in women, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
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http://dx.doi.org/10.1038/s41586-021-03779-7DOI Listing
August 2021

Mental health indicators and lung function following a large oil spill.

Eur Respir J 2021 Jul 29. Epub 2021 Jul 29.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

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http://dx.doi.org/10.1183/13993003.00712-2021DOI Listing
July 2021

Agricultural Pesticides and Shingles Risk in a Prospective Cohort of Licensed Pesticide Applicators.

Environ Health Perspect 2021 Jul 28;129(7):77005. Epub 2021 Jul 28.

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.

Background: Some pesticides are immunotoxic and have been associated with an increased risk of immune-mediated diseases. The risk of shingles, the clinical reactivation of varicella-zoster virus, increases with aging and immunosuppression; little is known about its associations with pesticides.

Objective: We examined the use of agricultural pesticides in relation to incident shingles in a prospective cohort of licensed pesticide applicators.

Methods: The study sample included 12,820 (97% male) farmers (enrolled in 1993-1997 in North Carolina and Iowa), who were followed for a median of 12 y (interquartile range: 11-13). Shingles was self-reported at enrollment and at follow-up. We evaluated ever-use of 48 agricultural pesticides reported at study enrollment in relation to shingles risk and considered exposure-response for intensity-weighted lifetime days (IWLDs) of use. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models, adjusting for state, and allowing estimates to vary by median attained age (60 y).

Results: Incident shingles was reported by 590 participants. Associations were positive () for ever- vs. never-use of eight insecticides, three fumigants, two fungicides, and five herbicides, and exposure-response trends were seen across increasing quartiles (Q3 and ) or tertiles (T3 and ) of IWLDs for four insecticides [permethrin (crops), coumaphos, malathion, and lindane], two fumigants (carbon tetrachloride/carbon disulfide and methyl bromide), and three herbicides [alachlor, trifluralin () and 2,4-dichlorophenoxyacetic acid]. Shingles was not associated with total years or days per year mixed or applied any pesticides, but in older participants, shingles was associated with a history of a high pesticide exposure event [ (95% CI: 1.45, 2.45)].

Conclusions: Several specific pesticides were associated with increased risk of shingles in farmers, especially at higher levels of cumulative use. These novel findings, if replicated in other populations, could have broader implications for the potential effects of pesticides on vaccine efficacy and susceptibility to other infections. https://doi.org/10.1289/EHP7797.
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http://dx.doi.org/10.1289/EHP7797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317610PMC
July 2021

The association between blood metals and hypertension in the GuLF study.

Environ Res 2021 Jul 23;202:111734. Epub 2021 Jul 23.

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA. Electronic address:

Background: Both essential and non-essential metals come from natural and anthropogenic sources. Metals can bioaccumulate in humans and may impact human health, including hypertension.

Methods: Blood metal (cadmium, lead, mercury, manganese, and selenium) concentrations were measured at baseline for a sample of participants in the Gulf Long-Term Follow-up (GuLF) Study. The GuLF Study is a prospective cohort study focused on potential health effects following the 2010 Deepwater Horizon oil spill. Hypertension was defined as high systolic (≥140 mm Hg) or diastolic (≥90 mm Hg) blood pressure or taking anti-hypertensive medications. A total of 957 participants who had blood measurement for at least one metal, baseline blood pressure measurements, information on any anti-hypertensive medication use, and relevant covariates were included in this cross-sectional analysis. We used Poisson regression to explore the association between individual blood metal levels and hypertension. Quantile-based g-computation was used to investigate the association between the metal mixture and hypertension. We also explored the association between individual blood metal levels and continuous blood pressure measurements using general linear regression.

Results: Comparing the highest quartile of blood metals with the lowest (Q4vs1), the hypertension prevalence ratio (PR) was 0.92 (95 % confidence interval (CI) = 0.73,1.15) for cadmium, 0.86 (95%CI = 0.66,1.12) for lead, 0.89 (95%CI = 0.71,1.12) for mercury, 1.00 (95%CI = 0.80,1.26) for selenium, and 1.22 (95%CI = 0.95,1.57) for manganese. We observed some qualitative differences across race and BMI strata although none of these differences were statistically significant. In stratified analyses, the PR (Q4vs1) for mercury was 0.69 (95%CI = 0.53, 0.91) in White participants and 1.29 (95%CI = 0.86,1.92) in Black participants (p for interaction = 0.5). The PR (Q4vs1) for manganese was relatively higher in Black participants (PR = 1.37, 95%CI = 0.92,2.05) than in White participants (PR = 1.15, 95%CI = 0.83,1.60, p for interaction = 0.5), with a suggestive dose-response among Blacks. After stratifying by obesity (BMI ≥30 and < 30), positive associations of of hypertension with cadmium (PR [Q4vs1] = 1.19, 95%CI = 0.91,1.56, p for interaction = 0.5), lead (PR [Q4vs1] = 1.14, 95%CI = 0.84,1.55, p for interaction = 1.0) and manganese (PR = 1.25, 95%CI = 0.93,1.68, p for interaction = 0.8) were observed in participants with BMI≥30, but not in participants with BMI<30. The joint effect of the metal mixture was 0.96 (95%CI = 0.73,1.27). We did not observe clear associations between blood metal levels and continuous blood pressure measurements.

Conclusion: We did not find overall cross-sectional associations between blood cadmium, lead, mercury, selenium levels and hypertension or blood pressure. We found some evidence suggesting that manganese might be positively associated with risk of hypertension. Associations varied somewhat by race and BMI.
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http://dx.doi.org/10.1016/j.envres.2021.111734DOI Listing
July 2021

Risk of Late-Onset Breast Cancer in Genetically Predisposed Women.

J Clin Oncol 2021 Jul 22:JCO2100531. Epub 2021 Jul 22.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years.

Methods: A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs.

Results: The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in , , and were found in 3.42% of women diagnosed with estrogen receptor (ER)-negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in , , , and were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in , , and .

Conclusion: This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with and PVs and perhaps with and PVs should be considered for magnetic resonance imaging screening.
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http://dx.doi.org/10.1200/JCO.21.00531DOI Listing
July 2021

The association between douching, genital talc use, and the risk of prevalent and incident cervical cancer.

Sci Rep 2021 Jul 21;11(1):14836. Epub 2021 Jul 21.

Epidemiology Branch, National Institute of Environmental Health Sciences, 111 TW Alexander Dr., Research Triangle Park, NC, 27709, USA.

While human papillomavirus is the primary cause of cervical cancer, other factors may influence susceptibility and response to the virus. Candidates include douching and talcum powder applied in the genital area. We used Cox proportional hazards models to estimate confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in the Sister Study (2003-2009), a US cohort of women aged 35-74. We considered pre-baseline (n = 523) and incident (n = 31) cervical cancers. Douching at ages 10-13 was positively associated with pre-baseline cervical cancer (HR 1.32, 95% CI 0.86-2.03), though the association was not statistically significant. We did not observe an association between adolescent talc use and pre-baseline cervical cancer (HR 0.95, 95% CI 0.76-1.19). Douching in the year before enrollment was positively associated with incident cervical cancer (HR 2.56, 95% CI 1.10-5.99). The association between recent genital talc use and incident cervical cancer was positive, but not statistically significant (HR 1.79, 95% CI 0.78-4.11). The observed positive association between douching and incident cervical cancer is consistent with previous retrospective case-control studies. In the first study to examine genital talc use and cervical cancer, we did not see evidence of an association.
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http://dx.doi.org/10.1038/s41598-021-94447-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295379PMC
July 2021

Association of neighborhood deprivation with pulmonary function measures among participants in the Gulf Long-Term Follow-up Study.

Environ Res 2021 Jul 17;202:111704. Epub 2021 Jul 17.

Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. Electronic address:

Introduction: Individual-level socioeconomic status (SES) has been shown to be an important determinant of lung function. Neighborhood level SES factors may increase psychological and physiologic stress and may also reflect other exposures that can adversely affect lung function, but few studies have considered neighborhood factors.

Objective: Our aim was to assess the association between neighborhood-level SES and lung function.

Methods: We cross-sectionally analyzed 6168 spirometry test results from participants in the Gulf long-term Follow-up Study, a large cohort of adults enrolled following the largest maritime oil spill in US history. Outcomes of interest included the forced expiratory volume in 1 s (FEV; mL), the forced vital capacity (FVC; mL), and the FEV/FVC ratio (%). Neighborhood deprivation was measured by linking participant home addresses to an existing Area Deprivation Index (ADI) and categorized into quartiles. Individual-level SES measures were collected at enrollment using a structured questionnaire and included income, educational attainment, and financial strain. We used multilevel regression to estimate associations between ADI quartiles and each lung function measure.

Results: Greater neighborhood deprivation was associated with lower FEV: β: -30 mL (95% CI: -97, 36), β: -70 mL (95% CI: -135, -4) and β: -104 mL (95% CI: -171, -36). FVC showed similar patterns of associations with neighborhood deprivation. No associations with the FEV/FVC ratio were observed.

Conclusion: Neighborhood deprivation, a measure incorporating economic and other stressors, was associated with lower FEV and FVC, with magnitudes of associations reaching clinically meaningful levels. The impact of this neighborhood SES measure persisted even after adjustment for individual-level SES factors.
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http://dx.doi.org/10.1016/j.envres.2021.111704DOI Listing
July 2021

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Nat Commun 2021 07 7;12(1):4198. Epub 2021 Jul 7.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
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http://dx.doi.org/10.1038/s41467-021-24327-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263739PMC
July 2021

Experiences with Everyday and Major Forms of Racial/Ethnic Discrimination and Type 2 Diabetes Risk among White, Black, and Hispanic/Latina Women: Findings from the Sister Study.

Am J Epidemiol 2021 Jul 2. Epub 2021 Jul 2.

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States.

Racial/ethnic discrimination may contribute to type 2 diabetes mellitus (T2DM) risk, but few studies have prospectively examined this relationship among racially/ethnically diverse populations. We analyzed prospective data from 33,833 eligible Sister Study participants enrolled from 2003 to 2009. In a follow-up questionnaire (2008-2012), participants reported lifetime experiences of everyday and major forms of racial/ethnic discrimination. Self-reported physician diagnoses of T2DM were ascertained until September 2017. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models, overall and stratified by race/ethnicity. Mean age (standard deviation) at enrollment was 54.9 (8.8) years, 90% self-identified as non-Hispanic (NH)-White, 7% NH-Black, and 3% Hispanic/Latina. Over an average of 7 years of follow-up, there were 1,167 incident cases of T2DM. NH-Black women most frequently reported everyday (75%) and major (51%) racial/ethnic discrimination (vs. 4% and 2% [NH-White] and 32% and 16% [Hispanic/Latina]). While everyday discrimination was not associated, experiencing major discrimination was marginally associated with higher T2DM risk overall (HR=1.26 [95% CI:0.99-1.61]) after adjustment for sociodemographic characteristics and body mass index. Associations were similar across racial/ethnic groups; however, racial/ethnic discrimination was more frequently reported among racial/ethnic minority women. Anti-discrimination efforts may help mitigate racial/ethnic disparities in T2DM risk.
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http://dx.doi.org/10.1093/aje/kwab189DOI Listing
July 2021

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Genome Biol 2021 06 29;22(1):194. Epub 2021 Jun 29.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.

Results: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.

Conclusion: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
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http://dx.doi.org/10.1186/s13059-021-02398-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243879PMC
June 2021

Methods for the Analysis of 26 Million VOC Area Measurements during the Deepwater Horizon Oil Spill Clean-up.

Ann Work Expo Health 2021 Jun 29. Epub 2021 Jun 29.

Exposure Assessment Applications, LLC, 6045 N. 27th. St., Arlington, VA 22207, USA.

The NIEHS GuLF STUDY is an epidemiologic study of the health of workers who participated in the 2010 Deepwater Horizon oil spill response and clean-up effort. Even with a large database of approximately 28 000 personal samples that were analyzed for total hydrocarbons (THCs) and other oil-related chemicals, resulting in nearly 160 000 full-shift personal measurements, there were still exposure scenarios where the number of measurements was too limited to rigorously assess exposures. Also available were over 26 million volatile organic compounds (VOCs) area air measurements of approximately 1-min duration, collected from direct-reading instruments on 38 large vessels generally located near the leaking well. This paper presents a strategy for converting the VOC database into hourly average air concentrations by vessel as the first step of a larger process designed to use these data to supplement full-shift THC personal exposure measurements. We applied a Bayesian method to account for measurements with values below the analytic instrument's limit of detection while processing the large database into average instrument-hour concentrations and then hourly concentrations across instruments on each day of measurement on each of the vessels. To illustrate this process, we present results on the drilling rig ship, the Discoverer Enterprise. The methods reduced the 26 million measurements to 21 900 hourly averages, which later contributed to the development of additional full-shift THC observations. The approach used here can be applied by occupational health professionals with large datasets of direct-reading instruments to better understand workplace exposures.
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http://dx.doi.org/10.1093/annweh/wxab038DOI Listing
June 2021

Use of hair products in relation to ovarian cancer risk.

Carcinogenesis 2021 Jun 26. Epub 2021 Jun 26.

Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC.

We evaluated whether hair products, which may contain carcinogens and endocrine disruptors that can be absorbed into the bloodstream, are related to ovarian cancer incidence in a prospective cohort. After excluding women with a history of ovarian cancer or bilateral oophorectomy, 40,559 Sister Study participants ages 35-74 at enrollment (2003-2009) were included. Participants completed questionnaires on hair product use, including hair dyes, straighteners/relaxers and permanents/body waves, in the past 12 months. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% Confidence Intervals (CIs) for the association between hair products and incident ovarian cancer. We assessed associations stratified by tumor type (serous, non-serous). Over a mean follow-up of 10 years, 241 women were diagnosed with ovarian cancer. Ever use of any of the examined hair products during the past year was not associated with ovarian cancer risk. However, frequent use (>4 times/year) of straighteners/relaxers or pressing products in the past year was associated with an increased risk of ovarian cancer (HR=2.19, 95% CI: 1.12-4.27). Ever use of permanent hair dye was positively associated with non-serous (HR=1.94, 95% CI 1.12-3.37), but inversely associated with serous (HR=0.65, 95% CI: 0.43-0.99) tumors (p-for-heterogeneity=0.002). Our novel findings suggest that frequent use of hair straighteners/relaxers or pressing products, which are primarily used by African American/Black women, and possibly permanent hair dye, may be associated with the occurrence of ovarian cancers.
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http://dx.doi.org/10.1093/carcin/bgab056DOI Listing
June 2021

Breast cancer risk factors and circulating anti-Müllerian hormone concentration in healthy premenopausal women.

J Clin Endocrinol Metab 2021 Jun 22. Epub 2021 Jun 22.

Department of Population Health, New York University School of Medicine, New York, NY.

Context: In a previous study we reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies.

Objective: Assess whether risk factors for breast cancer are correlates of AMH concentration.

Design: Cross-sectional.

Participants: 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49).

Setting: Ten cohort studies, general population.

Results: Adjusting for age and cohort, we observed positive associations of AMH with age at menarche (p<0.0001) and parity (p=0.0008), and an inverse association with hysterectomy/partial oophorectomy (p=0.0008). Compared to women of normal weight (BMI 18.5-24.9 kg/m 2, AMH was lower (relative geometric mean difference 27%, p<0.0001) among women who were obese (BMI>30). Current oral contraceptive use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, p<0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, p=0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40/≥40), associations of AMH with BMI and oral contraceptives were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (p-interaction<0.05).

Conclusion: This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and suggests that most of the associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.
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http://dx.doi.org/10.1210/clinem/dgab461DOI Listing
June 2021

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

Am J Hum Genet 2021 07 18;108(7):1190-1203. Epub 2021 Jun 18.

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10).
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http://dx.doi.org/10.1016/j.ajhg.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322933PMC
July 2021

Breast Cancer-Related Employment Disruption and Financial Hardship in the Sister Study.

JNCI Cancer Spectr 2021 Jun 17;5(3):pkab024. Epub 2021 Mar 17.

Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Chapel Hill, NC, USA.

Background: More than one-half of breast cancer cases are diagnosed among women aged younger than 62 years, which may result in employment challenges. This study examined whether cancer-related employment disruption was associated with increased financial hardship in a national US study of women with breast cancer.

Methods: Women with breast cancer who were enrolled in the Sister or Two Sister Studies completed a survivorship survey in 2012. Employment disruption was defined as stopping work completely or working fewer hours after diagnosis. Financial hardship was defined as: 1) experiencing financial problems paying for cancer care, 2) borrowing money or incurring debt, or 3) filing for bankruptcy because of cancer. Prevalence ratios and 95% confidence intervals for the association between employment disruption and financial hardship were estimated using multivariable Poisson regression with robust variance.

Results: We analyzed data from women employed at diagnosis (n = 1628). Women were a median age of 48 years at diagnosis and 5.6 years from diagnosis at survey completion. Overall, 27.3% of women reported employment disruption (15.4% stopped working; 11.9% reduced hours), and 21.0% experienced financial hardship (16.0% had difficulty paying for care; 12.6% borrowed money or incurred debt; 1.8% filed for bankruptcy). In adjusted analysis, employment disruption was associated with nearly twice the prevalence of financial hardship (prevalence ratio = 1.93, 95% confidence interval = 1.58 to 2.35).

Conclusions: Women experiencing employment disruptions after breast cancer may be more vulnerable to financial hardship. Findings highlight the need to target risk factors for employment disruption, facilitate return to work or ongoing employment, and mitigate financial consequences after cancer.
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http://dx.doi.org/10.1093/jncics/pkab024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178802PMC
June 2021

Risk of Breast Cancer Among Carriers of Pathogenic Variants in Breast Cancer Predisposition Genes Varies by Polygenic Risk Score.

J Clin Oncol 2021 Aug 8;39(23):2564-2573. Epub 2021 Jun 8.

Population Health Sciences Department, Weill Cornell Medicine, New York, NY.

Purpose: This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population.

Methods: A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in , , , , , , , , and . PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor-specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC.

Results: The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of , , and carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of and carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk.

Conclusion: PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of and nearly half of carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.
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http://dx.doi.org/10.1200/JCO.20.01992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330969PMC
August 2021

Early-life Farm Exposure and Ovarian Reserve in a US Cohort of Women.

Epidemiology 2021 Sep;32(5):672-680

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC.

Background: In a previous exploratory study, we reported lower concentrations of the ovarian reserve biomarker anti-Müllerian hormone (AMH) in adulthood with prenatal farm exposure. We now examine this association as well as childhood farm exposure using enrollment data from the Sister Study, a large US cohort of women.

Methods: We collected prenatal and childhood farm exposure data by questionnaire and telephone interview. However, serum AMH data were available only for a nested subset: premenopausal women ages 35-54 subsequently diagnosed with breast cancer (n = 418 cases) and their matched controls (n = 866). To avoid potential bias from restricting analyses to only premenopausal controls, we leveraged the available cohort data. We used data from both premenopausal cases and controls as well as postmenopausal women ages 35-54 (n = 3,526) (all presumed to have undetectable AMH concentrations) and applied weights to produce a sample representative of the cohort ages 35-54 (n = 17,799). The high proportion of undetectable AMH concentrations (41%) was addressed using reverse-scale Cox regression. An adjusted hazard ratio (HR) <1.0 indicates that exposed individuals had lower AMH concentrations than unexposed individuals.

Results: Prenatal exposure to maternal residence or work on a farm was associated with lower AMH concentrations (HR 0.66; 95% confidence intervals [CI] = 0.48 to 0.90). Associations between childhood farm residence exposures and AMH were null or weak, except childhood contact with pesticide-treated livestock or buildings (HR 0.69; 95% CI = 0.40 to 1.2).

Conclusions: Replication of the prenatal farm exposure and lower adult AMH association raises concern that aspects of prenatal farm exposure may result in reduced adult ovarian reserve.
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http://dx.doi.org/10.1097/EDE.0000000000001376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370468PMC
September 2021

Types and spatial contexts of neighborhood greenery matter in associations with weight status in women across 28 U.S. communities.

Environ Res 2021 08 19;199:111327. Epub 2021 May 19.

Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.

Excess body weight is a risk factor for many chronic diseases. Studies have identified neighborhood greenery as supportive of healthy weight. However, few have considered plausible effect pathways for ecosystem services (e.g., heat mitigation, landscape aesthetics, and venues for physical activities) or potential variations by climate. This study examined associations between weight status and neighborhood greenery that capture ecosystem services most relevant to weight status across 28 U.S. communities. Weight status was defined by body mass index (BMI) reported for 6591 women from the U.S. Sister Study cohort. Measures of greenery within street and circular areas at 500 m and 2000 m buffer distances from homes were derived for each participant using 1 m land cover data. Street area was defined as a 25 m-wide zone on both sides of street centerlines multiplied by the buffer distances, and circular area was the area of the circle centered on a home within each of the buffer distances. Measures of street greenery characterized the pedestrian environment to capture physically and visually accessible greenery for shade and aesthetics. Circular greenery was generated for comparison. Greenery types of tree and herbaceous cover were quantified separately, and a combined measure of tree and herbaceous cover (i.e., aggregate greenery) was also included. Mixed models accounting for the clustering at the community level were applied to evaluate the associations between neighborhood greenery and the odds of being overweight or obese (BMI > 25) with adjustment for covariates selected using gradient boosted regression trees. Analyses were stratified by climate zone (arid, continental, and temperate). Tree cover was consistently associated with decreased odds of being overweight or obese. For example, the adjusted odds ratio [AOR] was 0.92, 95% Confidence Interval [CI]: 0.88-0.96, given a 10% increase in street tree cover at the 2000 m buffer across the 28 U.S. communities. These associations held across climate zones, with the lowest AOR in the arid climate (AOR: 0.74, 95% CI: 0.54-1.01). In contrast, associations with herbaceous cover varied by climate zone. For the arid climate, a 10% increase in street herbaceous cover at the 2000 m buffer was associated with lower odds of being overweight or obese (AOR: 0.75, 95% CI: 0.55-1.03), whereas the association was reversed for the temperate climate, the odds increased (AOR: 1.19, 95% CI: 1.05-1.35). Associations between greenery and overweight/obesity varied by type and spatial context of greenery, and climate. Our findings add to a growing body of evidence that greenery design in urban planning can support public health. These findings also justify further defining the mechanism that underlies the observed associations.
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http://dx.doi.org/10.1016/j.envres.2021.111327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457404PMC
August 2021

Parkinson's disease case ascertainment in a large prospective cohort.

PLoS One 2021 19;16(5):e0251852. Epub 2021 May 19.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, United States of America.

Background: In epidemiologic studies where physician-based case adjudication is not feasible, Parkinson's disease (PD) case ascertainment is often limited to self-reports which may not be accurate. We evaluated strategies to identify PD cases in the Agricultural Health Study (AHS).

Methods: Doctor-diagnosed PD was self-reported on all cohort-wide surveys; potential cases were also identified from death certificates. Follow-up surveys asked about PD-related motor and non-motor symptoms. For PD confirmation, we collected additional diagnosis, symptom, and treatment data from 510 potential PD cases or their proxy (65% of those contacted) in a supplemental screener and obtained medical records for a subset (n = 65). We classified PD cases using established criteria and screener data.

Results: Of 510 potential PD cases, 75% were considered "probable" or "possible"; this proportion increased among participants diagnosed by a specialist (81.2%), taking PD medication (85.2%), or reporting ≥5 motor symptoms (86.8%) in a regular AHS survey. Of those with medical records, 93% (57 of 61) of probable or possible PD was confirmed. Never-smoking and non-motor and motor symptoms reported in prior AHS surveys were more common with probable/possible PD than unconfirmed PD.

Conclusion: In this retrospective PD case ascertainment effort, we found that PD self-report with information on motor symptoms or medications may be a reasonable alternative for identifying PD cases when physician exam is not feasible. Because of intervening mortality, screeners could not be obtained from about one-third of those contacted. Thus, findings warrant replication.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251852PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133399PMC
May 2021

Pesticide use and kidney function among farmers in the Biomarkers of Exposure and Effect in Agriculture study.

Environ Res 2021 08 11;199:111276. Epub 2021 May 11.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Electronic address:

Background: Pesticides have been reported to be associated with malignant and non-malignant kidney disease. Few studies have examined the relationship between individual pesticides and kidney dysfunction.

Objective: We evaluated the associations of pesticide use with measured kidney function among male pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a subcohort in the Agricultural Health Study.

Methods: Serum creatinine was measured in 1545 BEEA participants and estimated glomerular filtration rate (eGFR) was calculated with the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Using reported information on lifetime use of 41 pesticides, multivariable linear and logistic regression was used to examine associations with eGFR modeled continuously and with CKD (eGFR <60 mL/min/1.73 m), respectively. Models were adjusted for possible confounding factors related to kidney function and correlated pesticides.

Results: Lower eGFR was observed among pesticide applicators who ever used the herbicides pendimethalin (-3.7%, 95% confidence interval (CI): 5.8%, -1.5%), atrazine (-3.7%, 95% CI: 6.9%, -0.4%), and dicamba (-2.8%, 95% CI: 5.3%, -0.2%) compared with never users of each pesticide. Ever use of pendimethalin (odds ratio (OR)=1.6, 95% CI: 1.1, 2.2) and atrazine (OR=1.8, 95% CI: 1.0, 3.0) was also associated with elevated odds of CKD, with an exposure-response association between intensity-weighted lifetime days of pendimethalin use and CKD among active farmers (N=1302; p=0.04). Atrazine use within the last year was associated with lower eGFR and elevated odds of CKD when compared with never users, and we observed exposure-response associations with intensity-weighted lifetime days among recent users. Use of several other pesticides was associated with higher eGFR.

Discussion: These results suggest that two widely used herbicides, pendimethalin and atrazine, may be associated with altered kidney function among pesticide applicators. Our findings for these herbicides are consistent with observed associations with end-stage renal disease in the Agricultural Health Study.
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http://dx.doi.org/10.1016/j.envres.2021.111276DOI Listing
August 2021
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