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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.

Coagulopathies are commonly encountered in victims of pit viper envenomation. In the majority of patients these defects improve with administration of antivenin. However, blood products are often transfused based on arbitrary criteria and with significant risk to the patient. This article documents the effectiveness and risks of antivenin administration and the risks of blood product transfusion. We recommend that blood products not be used except for clearly defined clinical indications.