Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

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Background Evidence from previous studies suggests that women firefighters have greater risk of some adverse reproductive outcomes. The purpose of this study was to investigate whether women firefighters had greater risk of miscarriage compared to non-firefighters and whether there were occupational factors associated with risk of miscarriage among firefighters. Methods We studied pregnancies in the United States fire service using data from the Health and Wellness of Women Firefighters Study (n = 3181). We compared the prevalence of miscarriage among firefighters to published rates among non-firefighters using age-standardized prevalence ratios. We used generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs) between occupational factors (employment (career/volunteer), wildland firefighter status (wildland or wildland-urban-interface/structural), shift schedule, fire/rescue calls at pregnancy start) and risk of miscarriage, adjusted for age at pregnancy, education, gravidity, BMI, and smoking. We evaluated if associations varied by age at pregnancy or employment. Results Among 1074 firefighters and 1864 total pregnancies, 404 pregnancies resulted in miscarriages (22%). Among most recent pregnancies, 138 resulted in miscarriage (13%). Compared to a study of US nurses, firefighters had 2.33 times greater age-standardized prevalence of miscarriage (95% CI 1.96–2.75). Overall, we observed that volunteer firefighters had an increased risk of miscarriage which varied by wildland status (interaction p-value< 0.01). Among structural firefighters, volunteer firefighters had 1.42 times the risk of miscarriage (95% CI 1.11–1.80) compared to career firefighters. Among wildland/wildland-urban-interface firefighters, volunteer firefighters had 2.53 times the risk of miscarriage (95% CI 1.35–4.78) compared to career firefighters. Conclusions Age-standardized miscarriage prevalence among firefighters may be greater than non-firefighters and there may be variation in risk of miscarriage by fire service role. Further research is needed to clarify these associations to inform policy and decision-making.

Perinatal smoking, including smoking during pregnancy and postpartum smoking relapse, is a persistent public health problem. While childhood trauma has been linked to perinatal smoking, less is known about the association with more proximal stressful life events (SLEs). The objective of this study was to examine the association between SLEs that occurred during the year prior to childbirth with perinatal smoking. Using the Pregnancy Risk Assessment Monitoring System 2009–2011, perinatal smoking was assessed at three time points: (1) three months prior to pregnancy, (2) the last three months of pregnancy, and (3) two to six months postpartum. Survey respondents endorsed up to 13 SLEs (i.e., death of someone close). SLEs were analyzed individually, as well as using a cumulative score (range 0–13). Weighted analyses included unadjusted and adjusted logistic regression. Among those who smoked prior to pregnancy (n=15,316), 48% (n=7,308) reported quitting smoking during pregnancy. Of those, 44% (n=3,126) reported postpartum smoking relapse. A total of 11 SLEs were associated with smoking during pregnancy and 2 SLEs were associated with postpartum smoking relapse. The odds of continued smoking during pregnancy was 12% higher for each SLE endorsed (adjusted odds ratio [aOR] =1.12, 95% confidence interval [CI]: 1.09, 1.15) and this association was attenuated in relation to the odds of postpartum smoking relapse (aOR=1.03, 95% CI: 0.99, 1.08). SLEs are associated with perinatal smoking. Additional research is needed to elucidate the mechanisms of action and to develop interventions specific to the needs of women who experience SLEs.

Background Firefighters have increased cancer incidence and mortality rates compared to the general population, and are exposed to multiple products of combustion including known and suspected carcinogens. Objective The study objective was to quantify fire response exposures by role and self-reported exposure risks. Methods Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons (PAH-OHs) were measured at baseline and 2–4 h after structural fires and post-fire surveys were collected. Results Baseline urine samples were collected from 242 firefighters. Of these, 141 responded to at least one of 15 structural fires and provided a post-fire urine. Compared with baseline measurements, the mean fold change of post-fire urinary PAH-OHs increased similarly across roles, including captains (2.05 (95% CI 1.59–2.65)), engineers (2.10 (95% CI 1.47–3.05)), firefighters (2.83 (95% CI 2.14–3.71)), and paramedics (1.84 (95% CI 1.33–2.60)). Interior responses, smoke odor on skin, and lack of recent laundering or changing of hoods were significantly associated with increased post-fire urinary PAH-OHs. Significance Ambient smoke from the fire represents an exposure hazard for all individuals on the fireground; engineers and paramedics in particular may not be aware of the extent of their exposure. Post-fire surveys identified specific risks associated with increased exposure.

Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood samples from 45 incumbent and 41 new recruit non-smoking male firefighters and analyzed the samples for DNA methylation using an Illumina Methylation EPIC 850k chip. Adjusting for age and ethnicity, we performed: 1) genome-wide differential methylation analysis; 2) genome-wide prediction for firefighter status (incumbent or new recruit) and years of service; and 3) Ingenuity Pathway Analysis (IPA). Four CpGs, including three in the YIPF6, MPST, and PCED1B genes, demonstrated above 1.5-fold statistically significant differential methylation after Bonferroni correction. Genome-wide methylation predicted with high accuracy incumbent and new recruit status as well as years of service among incumbent firefighters. Using IPA, the top pathways with more than 5 gene members annotated from differentially methylated probes included Sirtuin signaling pathway, p53 signaling, and 5' AMP-activated protein kinase (AMPK) signaling. These DNA methylation findings suggest potential cellular mechanisms associated with increased cancer risk in firefighters.

Background Dysregulated microRNA (miRNA) expression could provide a mechanism linking firefighter exposure to increased cancer risk. Objective To determine if changes in longitudinal miRNA expression in firefighters are associated with occupational exposures. Methods Whole blood MiRNA was evaluated in 52 new recruits prior to live-fire training and 20–37 months later. Linear mixed effects models adjusted for age, ethnicity, BMI, and batch effects were used to determine associations separately for all fires and structure fires only between employment duration, cumulative fire-hours and fire-runs, and time since most recent fire with (1) nine a priori and (2) the full array of 799 miRNAs. Results For multivariable models including all fires, two a priori miRNAs were associated with employment duration and four with time since most recent fire. For multivariable models restricted to structure fires, three a priori miRNAs were associated with employment duration and one with fire-runs. Additional miRNAs from the full array were associated with employment duration for all fires and/or structure fires. In general, tumor suppressive miRNAs decreased and oncogenic miRNAs increased with exposure. Significance Changes in miRNAs may serve as biomarkers of exposure effects and a mechanism for increased cancer risk in firefighters.

Background Firefighters have occupational and environmental exposures to per‐ and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. Methods Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A–D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. Results In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A–C, sum of branched perfluoromethylheptane sulfonate isomers (Sm‐PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n‐PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n‐PFOA) was elevated in Departments B–D, and perfluorononanoate (PFNA) was elevated in Departments B–D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2‐(N‐methyl‐perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B–D. In female firefighters compared with NHANES, PFHxS and Sm‐PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. Conclusions Serum PFHxS, Sm‐PFOS, n‐PFOS, n‐PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.