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ObjectiveThe aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length.MethodsThe study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States.ResultsIncumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality.ConclusionsLong-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.

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.

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.

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.

ObjectivesFirefighters face exposures associated with adverse health outcomes including risk for multiple cancers. DNA methylation, one type of epigenetic regulation, provides a potential mechanism linking occupational hazards to adverse health outcomes. We hypothesised that DNA methylation profiles would change in firefighters after starting their service and that these patterns would be associated with occupational exposures (cumulative fire-hours and fire-runs).MethodsWe profiled DNA methylation with the Infinium MethylationEPIC in blood leucocytes at two time points in non-smoking new recruits: prior to live fire training and 20–37 months later. Linear mixed effects models adjusted for potential confounders were used to identify differentially methylated CpG sites over time using data from 50 individuals passing all quality control.ResultsWe report 680 CpG sites with altered methylation (q value ConclusionsOverall, this study provides evidence that DNA methylation may be altered by fireground exposures, and the impact of this change on disease development should be evaluated.

Objective/Background: Fire service shift workers are at risk of developing mental health difficulties related to sleep loss and emotion dysregulation. We aimed to clarify the relationship between off-shift recovery sleep and emotion regulation on stress, fatigue and irritability. Participants: A total of 61 fire service shift workers (e.g. firefighter, captain, engineer, paramedic) on a "5/6" shift. Methods: Following five 24-hour shifts, participants reported on emotion regulation as well as daily sleep, stress, fatigue and irritability during six consecutive off-shift recovery days. Mediation analyses examined (1) emotion regulation as a predictor and sleep as a mediator of stress, fatigue and irritability outcomes; and (2) sleep as a predictor and emotion regulation as a mediator of stress, fatigue and irritability outcomes. Results: Greater self-reported total sleep time predicted lower recovery stress, fatigue, and irritability. Greater subjective sleep efficiency predicted lower recovery stress and fatigue, but not irritability. No significant relationships emerged for objective sleep or emotion regulation variables predicting stress, fatigue or irritability. There were no significant findings with either emotion regulation or sleep variables included as mediators. Conclusions: These findings suggest that stress management programs for fire service shift workers may be most effective when targeting sleep efficiency and quantity rather than emotion regulation strategies in the off-shift recovery period.

Objectives: Firefighters have elevated cancer incidence and mortality rates. MicroRNAs play prominent roles in carcinogenesis, but have not been previously evaluated in firefighters. Methods: Blood from 52 incumbent and 45 new recruit nonsmoking firefighters was analyzed for microRNA expression, and the results adjusted for age, obesity, ethnicity, and multiple comparisons. Results: Nine microRNAs were identified with at least a 1.5-fold significant difference between groups. All six microRNAs with decreased expression in incumbent firefighters have been reported to have tumor suppressor activity or are associated with cancer survival, and two of the three microRNAs with increased expression in incumbent firefighters have activities consistent with cancer promotion, with the remaining microRNA associated with neurological disease. Conclusion: Incumbent firefighters showed differential microRNA expression compared with new recruits, providing potential mechanisms for increased cancer risk in firefighters.

Objective Evaluate the effectiveness of firefighter exposure reduction interventions. Methods Fireground interventions included use of self-contained breathing apparatus by engineers, entry team wash down, contaminated equipment isolation, and personnel showering and washing of gear upon return to station. Urinary polycyclic aromatic hydrocarbon metabolites (PAH-OHs) were measured after structural fire responses before and after intervention implementation. Separately, infrared sauna use following live-fire training was compared to standard postfire care in a randomized trial. Results The fireground interventions significantly reduced mean total urinary postfire PAH-OHs in engineers (-40.4%, 95%CI -63.9%, -2.3%) and firefighters (-36.2%, 95%CI -56.7%, -6.0%) but not captains (-11.3% 95%CI -39.4%, 29.9%). Sauna treatment non-significantly reduced total mean PAH-OHs by -43.5% (95%CI -68.8%, 2.2%). Conclusions The selected fireground interventions reduced urinary PAH-OHs in engineers and firefighters. Further evaluation of infrared sauna treatment is needed.

Introduction Cancer is a leading cause of fire service morbidity and mortality. Measurement of urinary polycyclic aromatic hydrocarbons (PAHs), a group which includes known carcinogens, provides a means of evaluating absorption from all exposure routes. Activation of the aryl hydrocarbon receptor (AhR) and p53 pathways is associated with cancer, and their evaluation through in vitro urinary bioassays provides measures of toxicity of the chemical mixtures to which firefighters are exposed. Methods Urine was collected at baseline and two hours after responding to fires in 80 Tucson firefighters. Urine contaminants were de-conjugated using β-Glucuronidase and extracted using Focus Solid Phase Extraction (SPE) cartridges. Quantification of hydroxylated PAH (PAH-OH) target analytes was conducted with GC-MS/MS. In addition, the urinary extracts were evaluated using AhR and p53 in vitro bioassays. Results Compared to baseline, structural firefighting was associated with an increase in urinary PAH-OH concentrations. Increased concentrations were also found in training fires when self-contained breathing apparatus (SCBA) were used assiduously, suggesting a primary route of dermal exposure in that setting. Contrary to expectations, engineers (vehicle drivers) also demonstrated increased urinary PAH-OH concentrations, which was felt to be due to inhalation exposure as they generally did not wear SCBA. AhR and p53 activation occurred in general with higher concentrations of PAH-OHs in the urine, but extent of activation was not highly correlated with any single urinary PAH-OH marker. Conclusion Among firefighters, urinary PAH-OH concentrations increase in both entry teams and engineers. The route and extent of dermal and inhalation exposure vary with the specific job task at the fireground. AhR and p53 in vitro bioassays demonstrate activation of cancer pathways following occupational exposure in firefighters.

Introduction Firefighters are exposed to carcinogens and have elevated cancer rates. Cancer may be caused by activation of oncogenes or inhibition of tumour suppressor genes, such as through alterations in microRNA (miRNA) concentrations and DNA methylation. We hypothesised that occupational exposures in firefighters would lead to epigenetic changes associated with activation of cancer pathways and increased cancer risk. We designed this study to compare epigenetic changes in incumbent firefighters and new recruits. Methods At the time of subject selection, the study population consisted of 119 incumbents and 70 recruits. From this group, 108 subjects were randomly selected for miRNA analysis and 96 for DNA methylation analysis, both evenly divided among incumbents and recruits. Only non-smoker male firefighters were included in the final comparison. MiRNAs and DNA methylation were measured with the nCounter Human v3 miRNA expression assay with over 828 miRNAs and the Illumina MethylationEPIC 850 k chips, respectively. Result After adjusting for age and BMI, miR-1260a, miR-145–5 p, miR-181c-5p, miR-331–3 p, miR-361–5 p, and miR584–3 p were significantly downregulated in incumbent firefighters. MiR-208b-5p, miR-30e-3p, and miR-486–3 p were significantly overexpressed in incumbents. Controlling the genome-wide false discovery rate at 5%, 22 CpGs were annotated to promoter regions of a gene and were hypermethylated in the incumbents including YIPF6, HELB, SYT5 and DVL2. Discussion MiR-181c-5p, miR-145–5 p, and miR-584–3 p are involved in tumour suppression. MiR-30e-3p is upregulated in skin cancer and is a poor prognostic factor in lung cancer. Co-amplification of the YIPF6 gene with the androgen receptor may stimulate prostate tumour progression. Aberrant activation of HELB reduces genomic stability, a hallmark of cancer. SYT may have a novel function in breast cancer. DVL2 is a part of the Wnt signalling pathway involved in multiple cancers. These epigenetic biomarkers of carcinogenic exposure in firefighters should be further evaluated in larger studies.

Introduction Recent epidemiologic studies in the United States have demonstrated excess mortality rates for cancer in firefighters compared with the general population. Firefighters are exposed to multiple carcinogens in the workplace through skin contamination and inhalation. However, we currently do not understand which individual exposures are responsible for cancer in firefighters, the mechanisms by which these exposures cause cancer, or effective means of reducing exposures. Development of a large multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Methods The study is harmonising existing firefighter cohort studies in Arizona and Florida, and expanding to include the Boston Fire Department and volunteer and combination fire departments. The study framework components include an Oversight and Planning Board (OPB), a Data Coordination Centre (DCC), an Exposure Assessment Centre (EAC) and a Biomarker Analysis Centre (BAC). Results The OPB is providing oversight of the study through collaboration with fire service organisations and government agencies. The DCC is developing standardised participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. The EAC is developing a carcinogen exposure matrix using self-reported and quantitative exposure measurements to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. The BAC is carrying out pilot studies of epigenetic markers of carcinogenic effect and cancer risk comparing firefighters with a range of cumulative exposures and non-firefighter controls. Conclusion A framework is being established for the subsequent development of a large multicenter cohort study of cancer in the fire service; advance our understanding of firefighter exposures to carcinogens; and help identify biomarkers of carcinogen effect and cancer risk.