Endocrine disrupting chemical mixture exposure and risk of papillary thyroid cancer in U.S. military personnel: A nested case-control study.

Single-pollutant methods to evaluate associations between endocrine disrupting chemicals (EDCs) and thyroid cancer risk may not reflect realistic human exposures. Therefore, we evaluated associations between exposure to a mixture of 18 EDCs, including polychlorinated biphenyls (PCBs), brominated flame retardants, and organochlorine pesticides, and risk of papillary thyroid cancer (PTC), the most common thyroid cancer histological subtype. We conducted a nested case-control study among U.S. military servicemembers of 652 histologically-confirmed PTC cases diagnosed between 2000 and 2013 and 652 controls, matched on birth year, sex, race/ethnicity, military component (active duty/reserve), and serum sample timing. We estimated mixture odds ratios (OR), 95% confidence intervals (95% CI), and standard errors (SE) for associations between pre-diagnostic serum EDC mixture concentrations, overall PTC risk, and risk of histological subtypes of PTC (classical, follicular), adjusted for body mass index and military branch, using quantile g-computation. Additionally, we identified relative contributions of individual mixture components to PTC risk, represented by positive and negative weights (w). A one-quartile increase in the serum mixture concentration was associated with a non-statistically significant increase in overall PTC risk (OR = 1.19; 95% CI = 0.91, 1.56; SE = 0.14). Stratified by histological subtype and race (White, Black), a one-quartile increase in the mixture was associated with increased classical PTC risk among those of White race (OR = 1.59; 95% CI = 1.06, 2.40; SE = 0.21), but not of Black race (OR = 0.95; 95% CI = 0.34, 2.68; SE = 0.53). PCBs 180, 199, and 118 had the greatest positive weights driving this association among those of White race (w = 0.312, 0.255, and 0.119, respectively). Findings suggest that exposure to an EDC mixture may be associated with increased classical PTC risk. These findings warrant further investigation in other study populations to better understand PTC risk by histological subtype and race.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Health outcomes among offspring of US Coast Guard responders to the Deepwater Horizon oil spill, 2010-2011.

OBJECTIVE: To evaluate the potential for adverse health outcomes among infants born to US Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill disaster. METHODS: Department of Defense Birth and Infant Health Research programme data identified a cohort of singleton infants born 2010-2011 to USCG personnel in the DWH Oil Spill Coast Guard Cohort study. Infants were included if their military parent ('sponsor') responded to the oil spill during a selected reproductive exposure window (ie, 3 months preconception for male sponsors and periconception through pregnancy for female sponsors), or if their sponsor was a non-responder. χ2 tests and multivariable log-binomial regression were used to compare the demographic and health characteristics of infants born to spill responders and non-responders. RESULTS: Overall, 1974 infants with a male sponsor (n=182 responder, n=1792 non-responder) and 628 infants with a female sponsor (n=35 responder, n=593 non-responder) in the DWH Oil Spill Coast Guard Cohort were identified. Health outcomes were similar among the offspring of male responders and non-responders. The frequency of any poor live birth outcome (ie, low birth weight, preterm birth or birth defect) was higher among infants born to female responders (17.1%, n=6) than non-responders (8.9%, n=53); the maternal age-adjusted association was suggestively elevated (risk ratio 1.93, 95% CI 0.89 to 4.16). CONCLUSION: Infant health outcomes were comparable between the offspring of male USCG oil spill responders and non-responders. Findings were limited by the small number of infants identified, particularly among female responders, and should be interpreted with caution.

Risk of longer-term neurological conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort Study - Five years of follow-up.

BACKGROUND: Long-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill. METHODS: We used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010-2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking. RESULTS: Compared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only. CONCLUSION: In this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions.

Exposure patterns among Coast Guard responders to the Deepwater Horizon Oil Spill: A latent class analysis.

Background: The Deepwater Horizon Oil Spill was an environmental crisis for which multiple groups, including the United States Coast Guard (USCG), provided emergency response services. A cohort of 5,665 USCG oil spill responders completed postdeployment surveys eliciting information on a variety of topics, including oil spill-related exposures and experiences. Our objective was to determine the most common exposure patterns among USCG responders. Methods: We used latent class analysis based on six indicator variables reflecting different aspects of the responders' experiences: exposure to oil, exposure to engine exhaust fumes or carbon monoxide, hand sanitizer use, sunblock use, mosquito bites, and level of anxiety. We validated our interpretation of these latent classes using ancillary variables. Results: The model distinguished four distinct exposure profiles, which we interpreted as "low overall exposure" (prevalence estimate = 0.18), "low crude oil/exhaust and moderate time outdoors/anxiety (prevalence estimate = 0.18), "high crude oil/exhaust and moderate time outdoors/anxiety" (prevalence estimate = 0.25), and "high overall exposure" (prevalence estimate = 0.38). The validation analysis was consistent with our interpretation of the latent classes. Conclusions: The exposure patterns identified in this analysis can help inform future studies of the health impacts of exposure mixtures among USCG oil spill responders.

A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members.

BACKGROUND AND OBJECTIVES: Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype. METHODS: We carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC. RESULTS: Four PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis. DISCUSSION: This study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Risk factors for acute mental health symptoms and tobacco initiation in Coast Guard Responders to the Deepwater Horizon oil spill.

Acute mental health symptoms experienced during oil spill response work are understudied, especially among nonlocal responders. We assessed potential risk factors for acute mental health symptoms and tobacco initiation among U.S. Coast Guard responders to the 2010 Deepwater Horizon (DWH) oil spill who completed a deployment exit survey. Cross-sectional associations among responder characteristics, deployment-related stressors (deployment duration, timing, crude oil exposure, physical symptoms, injuries), and professional help-seeking for stressors experienced with concurrent depression/anxiety and tobacco initiation were examined. Log-binomial regression was used to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals. Sensitivity analyses excluded responders with a history of mental health conditions using health encounter data from the Military Health System Data Repository. Of the 4,855 responders, 75.5% were deployed from nonlocal/non-Gulf home stations, 5.8% reported concurrent depression and anxiety, and 2.8% reported the initiation of any tobacco product during oil spill response. Self-report of concurrent depression and anxiety was more prevalent among female responders and positively associated with longer deployments, crude oil exposure via inhalation, physical symptoms and injuries, and professional help-seeking during deployment, aPRs = 1.54-6.55. Tobacco initiation was inversely associated with older age and officer rank and positively associated with deployment-related stressors and depression/anxiety during deployment, aPRs = 1.58-4.44. Associations remained robust after excluding responders with a history of mental health- and tobacco-related health encounters up to 3 years before deployment. Depression, anxiety, and tobacco initiation were cross-sectionally associated with oil spill response work experiences among DWH responders, who largely originated outside of the affected community.

Acute and longer-term cardiovascular conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort.

INTRODUCTION: In 2010, the U.S. Coast Guard (USCG) led a clean-up response to the Deepwater Horizon (DWH) oil spill. Human studies evaluating acute and longer-term cardiovascular conditions associated with oil spill-related exposures are sparse. Thus, we aimed to investigate prevalent and incident cardiovascular symptoms/conditions in the DHW Oil Spill Coast Guard Cohort. METHODS: Self-reported oil spill exposures and cardiovascular symptoms were ascertained from post-deployment surveys (n = 4,885). For all active-duty cohort members (n = 45,193), prospective cardiovascular outcomes were classified via International Classification of Diseases, 9th Edition from military health encounter records up to 5.5 years post-DWH. We used log-binomial regression to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) in the cross-sectional analyses and Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% CIs for incident cardiovascular diagnoses during 2010-2015 and stratifying by earlier (2010-2012) and later (2013-2015) time periods. RESULTS: Prevalence of chest pain was associated with increasing levels of crude oil exposure via inhalation (aPRhigh vs. none = 2.00, 95% CI = 1.16-3.42, p-trend = 0.03) and direct skin contact (aPRhigh vs. none = 2.72, 95% CI = 1.30-5.16, p-trend = 0.03). Similar associations were observed for sudden heartbeat changes and for being in the vicinity of burning oil exposure. In prospective analyses, responders (vs. non-responders) had an elevated risk for mitral valve disorders during 2013-2015 (aHR = 2.12, 95% CI = 1.15-3.90). Responders reporting ever (vs. never) crude oil inhalation exposure were at increased risk for essential hypertension, particularly benign essential hypertension during 2010-2012 (aHR = 2.00, 95% CI = 1.08-3.69). Responders with crude oil inhalation exposure also had an elevated risk for palpitations during 2013-2015 (aHR = 2.54, 95% CI = 1.36-4.74). Cardiovascular symptoms/conditions aPR and aHR estimates were generally stronger among responders reporting exposure to both crude oil and oil dispersants than among those reporting neither. CONCLUSIONS: In this large study of the DWH oil spill USCG responders, self-reported spill clean-up exposures were associated with acute and longer-term cardiovascular symptoms/conditions.

Incidence of chronic respiratory conditions among oil spill responders: Five years of follow-up in the Deepwater Horizon Oil Spill Coast Guard Cohort study.

BACKGROUND: Over ten years after the Deepwater Horizon (DWH) oil spill, our understanding of long term respiratory health risks associated with oil spill response exposures is limited. We conducted a prospective analysis in a cohort of U.S. Coast Guard personnel with universal military healthcare. METHODS: For all active duty cohort members (N = 45,193) in the DWH Oil Spill Coast Guard Cohort Study we obtained medical encounter data from October 01, 2007 to September 30, 2015 (i.e., ~2.5 years pre-spill; ~5.5 years post-spill). We used Cox Proportional Hazards regressions to calculate adjusted hazard ratios (aHR), comparing risks for incident respiratory conditions/symptoms (2010-2015) for: responders vs. non-responders; responders reporting crude oil exposure, any inhalation of crude oil vapors, and being in the vicinity of burning crude oil versus responders without those exposures. We also evaluated self-reported crude oil and oil dispersant exposures, combined. Within-responder comparisons were adjusted for age, sex, and smoking. RESULTS: While elevated aHRs for responder/non-responder comparisons were generally weak, within-responder comparisons showed stronger risks with exposure to crude oil. Notably, for responders reporting exposure to crude oil via inhalation, there were elevated risks for allsinusitis (aHR = 1.48; 95%CI, 1.06-2.06), unspecified chronic sinusitis (aHR = 1.55; 95%CI, 1.08-2.22), chronic obstructive pulmonary disease (COPD) and other allied conditions (aHR = 1.43; 95%CI, 1.00-2.06), and dyspnea and respiratory abnormalities (aHR = 1.29; 95%CI, 1.00-1.67); there was a suggestion of elevated risk for diseases classified as asthma and reactive airway diseases (aHR = 1.18; 95%CI, 0.98-1.41), including the specific condition, asthma (aHR = 1.35; 95%CI, 0.80-2.27), the symptom, shortness of breath (aHR = 1.50; 95%CI, 0.89-2.54), and the overall classification of chronic respiratory conditions (aHR = 1.18; 95%CI, 0.98-1.43). Exposure to both crude oil and dispersant was positively associated with elevated risk for shortness of breath (HR = 2.24; 95%CI, 1.09-4.64). CONCLUSIONS: Among active duty Coast Guard personnel, oil spill clean-up exposures were associated with moderately increased risk for longer term respiratory conditions.

A review of the toxicology of oil in vertebrates: what we have learned following the Deepwater Horizon oil spill.

In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.

Neurological symptoms associated with oil spill response exposures: Results from the Deepwater Horizon Oil Spill Coast Guard Cohort Study.

INTRODUCTION: The Deepwater Horizon (DWH) oil spill was the largest marine oil spill in U.S. history, involving the response of tens of thousands clean-up workers. Over 8500 United States Coast Guard personnel were deployed in response to the spill. Little is understood about the acute neurological effects of oil spill clean-up-related exposures. Given the large number of people involved in large oil spill clean-ups, study of these effects is warranted. METHODS: We utilized exposure, health, and lifestyle data from a post-deployment survey administered to Coast Guard responders to the DWH oil spill. Crude oil exposure was assessed via self-reported inhalation and skin contact metrics, categorized by frequency of self-reported exposure to crude oil during deployment (never, rarely, sometimes, most/all of the time). Combined exposure to crude oil and oil dispersant was also evaluated. Adjusted log binomial regressions were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI), investigating the associations between oil spill exposures and neurological symptoms during deployment. Stratified analyses investigated potential effect modification by sex, exhaust fume exposure, personal protective equipment (PPE) use, and deployment duration and timing. RESULTS: Increasing frequency of crude oil exposure via inhalation was associated with increased likelihood of headaches (PRmost/all vs. never = 1.80), lightheadedness (PRmost/all vs. never = 3.36), difficulty concentrating (PRmost/all vs. never = 1.72), numbness/tingling sensation (PRmost/all vs. never = 3.32), blurred vision (PRmost/all vs. never = 2.87), and memory loss/confusion (PRmost/all vs. never = 2.03), with significant tests for trend. Similar results were found for crude oil exposure via skin contact. Exposure to both oil and oil dispersants yielded associations that were appreciably greater in magnitude than for oil alone for all neurological symptoms. Sensitivity analyses excluding responders in the highest environmental heat categories and responders with relevant pre-existing conditions indicated robustness of these results. Stratified analyses indicated possible effect modification by sex, PPE use, and heat exposure. CONCLUSIONS: This study provides evidence of a cross sectional association between crude oil exposures and acute neurological symptoms in a sample of U.S. Coast Guard responders. Additionally, it suggests that exposure to both crude oil and oil dispersant may result in stronger associations and that heat may interact synergistically with oil exposures resulting in more acute neurological symptoms. Future investigations are needed to confirm these findings.

Environmental Heat Exposure and Heat-Related Symptoms in United States Coast Guard Deepwater Horizon Disaster Responders.

OBJECTIVES: The response to the 2010 Deepwater Horizon oil spill was impacted by heat. We evaluated the association between environmental heat exposure and self-reported heat-related symptoms in US Coast Guard Deepwater Horizon disaster responders. METHODS: Utilizing climate data and postdeployment survey responses from 3648 responders, we assigned heat exposure categories based on both wet bulb globe temperature (WBGT) and heat index (HI) measurements (median, mean, maximum). We calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) via adjusted Poisson regression models with robust error variance to estimate associations with reported heat-related symptoms. We also evaluated the association between use of personal protective equipment (PPE) and heat-related symptoms. RESULTS: Those in the highest WBGT median-based heat exposure category had increased prevalence of heat-related symptoms compared to those in the lowest category (PR=2.22 [95% CI: 1.61, 3.06]), and there was a significant exposure-response trend (P<.001). Results were similar for exposure categories based on WBGT and HI metrics. Analyses stratified by use of PPE found significantly stronger associations between environmental heat exposure and heat-related symptoms in those who did not use PPE (PR=2.23 [95% CI: 1.10, 4.51]) than in those who did (PR=1.64 [95% CI: 1.14, 2.36]). CONCLUSIONS: US Coast Guard Deepwater Horizon disaster responders who experienced higher levels of environmental heat had higher prevalences of heat-related symptoms. These symptoms may impact health, safety, and mission effectiveness. As global climate change increases the frequency of disasters and weather extremes, actions must be taken to prevent heat-related health impacts among disaster responders. (Disaster Med Public Health Preparedness. 2019;13:561-569).

The deepwater horizon oil spill coast guard cohort study: A cross-sectional study of acute respiratory health symptoms.

INTRODUCTION: Over 8500 United States Coast Guard (USCG) personnel were deployed in response to the Deepwater Horizon (DWH) oil spill; however, human respiratory effects as a result of spill-related exposures are relatively unknown. METHODS: USCG personnel who responded to the DWH oil spill were queried via survey on exposures to crude oil and oil dispersant, and acute respiratory symptoms experienced during deployment. Adjusted log binomial regressions were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI), investigating the associations between oil spill exposures and respiratory symptoms. RESULTS: 4855 USCG personnel completed the survey. More than half (54.6%) and almost one-fourth (22.0%) of responders were exposed to crude oil and oil dispersants, respectively. Coughing was the most prevalent symptom (19.4%), followed by shortness of breath (5.5%), and wheezing (3.6%). Adjusted analyses showed an exposure-response relationship between increasing deployment duration and likelihood of coughing, shortness of breath, and wheezing in the pre-capping period. A similar pattern was observed in the post-capping period for coughing and wheezing. Adjusted analyses revealed increased PRs for coughing (PR=1.92), shortness of breath (PR=2.60), and wheezing (PR=2.68) for any oil exposure. Increasing frequency of inhalation of oil was associated with increased likelihood of all three respiratory symptoms. A similar pattern was observed for contact with oil dispersants for coughing and shortness of breath. The combination of both oil and oil dispersants presented associations that were much greater in magnitude than oil alone for coughing (PR=2.72), shortness of breath (PR=4.65), and wheezing (PR=5.06). CONCLUSIONS: Results from the present study suggested strong relationships between oil and oil dispersant exposures and acute respiratory symptoms among disaster responders. Future prospective studies will be needed to confirm these findings.

High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study.

Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc.

Cancer incidence and metolachlor use in the Agricultural Health Study: An update.

Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-1997. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n = 5,701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors.

Disaster-related exposures and health effects among US Coast Guard responders to Hurricanes Katrina and Rita: a cross-sectional study.

OBJECTIVE: Disaster responders work among poorly characterized physical and psychological hazards with little understood regarding health consequences of their work. METHODS: A survey administered to 2834 US Coast Guard responders to Hurricanes Katrina and Rita provided data on exposures and health effects. Prevalence odds ratios (PORs) evaluated associations between baseline characteristics, missions, exposures, and health effects. RESULTS: Most frequent exposures were animal/insect vector (n = 1309; 46%) and floodwater (n = 817; 29%). Most frequent health effects were sunburn (n = 1119; 39%) and heat stress (n = 810; 30%). Significant positive associations were for mold exposure and sinus infection (POR = 10.39); carbon monoxide and confusion (POR = 6.27); lack of sleep and slips, trips, falls (POR = 3.34) and depression (POR = 3.01); being a Gulf-state responder and depression (POR = 3.22). CONCLUSIONS: Increasing protection for disaster responders requires provisions for adequate sleep, personal protective equipment, and access to medical and psychological support.

PTSD and DNA Methylation in Select Immune Function Gene Promoter Regions: A Repeated Measures Case-Control Study of U.S. Military Service Members.

BACKGROUND: The underlying molecular mechanisms of PTSD are largely unknown. Distinct expression signatures for PTSD have been found, in particular for immune activation transcripts. DNA methylation may be significant in the pathophysiology of PTSD, since the process is intrinsically linked to gene expression. We evaluated temporal changes in DNA methylation in select promoter regions of immune system-related genes in U.S. military service members with a PTSD diagnosis, pre- and post-diagnosis, and in controls. METHODS: Cases (n = 75) had a post-deployment diagnosis of PTSD in their medical record. Controls (n = 75) were randomly selected service members with no PTSD diagnosis. DNA was extracted from pre- and post-deployment sera. DNA methylation (%5-mC) was quantified at specific CpG sites in promoter regions of insulin-like growth factor 2 (IGF2), long non-coding RNA transcript H19, interleukin-8 (IL8), IL16, and IL18 via pyrosequencing. We used multivariate analysis of variance and generalized linear models to calculate adjusted means (adjusted for age, gender, and race) to make temporal comparisons of %5-mC for cases (pre- to post-deployment) versus controls (pre- to post-deployment). RESULTS: There were significant differences in the change of %5-mC pre- to post-deployment between cases and controls for H19 (cases: +0.57%, controls: -1.97%; p = 0.04) and IL18 (cases: +1.39%, controls: -3.83%; p = 0.01). For H19 the difference was driven by a significant reduction in %5-mC among controls; for IL18 the difference was driven by both a reduction in %5-mC among controls and an increase in %5-mC among cases. Stratified analyses revealed more pronounced differences in the adjusted means of pre-post H19 and IL18 methylation differences for cases versus controls among older service members, males, service members of white race, and those with shorter deployments (6-12 months). CONCLUSION: In the study of deployed personnel, those who did not develop PTSD had reduced %5-mC levels of H19 and IL18 after deployment, while those who did develop PTSD had increased levels of IL18. Additionally, pre-deployment the people who later became cases had lower levels of IL18 %5-mC compared with controls. These findings are preliminary and should be investigated in larger studies.

DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members.

AIM: We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq. METHODS: Cases (n = 75) had a postdeployment diagnosis of PTSD. Controls (n = 75) were randomly selected service members with no postdeployment PTSD diagnosis. Pre- and post-deployment sera were accessed, DNA was extracted and DNA methylation (percentage 5-methyl cytosine) was quantified via pyrosequencing. Conditional and unconditional logistic regressions were used to compare: cases post- to pre-deployment; controls post- to pre-deployment; cases to controls predeployment; cases to controls postdeployment. RESULTS: LINE-1 was hypermethylated in controls post- versus pre-deployment (odds ratio [OR]: 1.33; 95% CI: 1.06-1.65) and hypomethylated in cases versus controls postdeployment (OR: 0.82; 95% CI: 0.67-1.01). Alu was hypermethylated for cases versus controls predeployment (OR: 1.46; 95% CI: 1.08-1.97). CONCLUSION: Patterns of hypermethylation of LINE-1 in controls postdeployment and of Alu in cases postdeployment are intriguing and may suggest resilience or vulnerability factors.

Global DNA methylation and tumor suppressor gene promoter methylation and gastric cancer risk in an Omani Arab population.

AIM: We carried out a case-control study in an Omani Arab population to investigate the association between gastric cancer and peripheral blood leukocyte DNA methylation in LINE-1 and in the tumor suppressor genes CDH1, p16, TP53 and RUNX3. MATERIALS & METHODS: We quantified methylation (%5-mC) in DNA extracted from peripheral blood leukocytes via pyrosequencing. We calculated odds ratios (ORs) and 95% CIs using logistic regression. RESULTS: We found patterns of global hypomethylation (LINE-1: OR(continuous) = 0.59; 95% CI: 0.42-0.82) and TP53 promoter hypomethylation (OR(continuous) = 0.64; 95% CI: 0.16-0.85) for cases versus controls; p16 promoter region hypomethylation was not statistically significant. Evaluating LINE-1, TP53 and p16 jointly yielded a more pronounced negative association with gastric cancer (OR: 0.24; 95% CI: 0.09-0.66). Age was a significant effect modifier. We found no differences by tumor grade, stage or histology. CONCLUSION: We found a pattern of global hypomethylation and promoter region hypomethylation of TP53 and p16 in cases versus controls for this population of Omani Arabs.

Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994-2007).

BACKGROUND: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association. METHODS: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure. RESULTS: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic. CONCLUSIONS: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.