Article Text
Abstract
Objectives Firefighters 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).
Methods We 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.
Results We report 680 CpG sites with altered methylation (q value <0.05) including 60 with at least a 5% methylation difference at follow-up. Genes with differentially methylated CpG sites were enriched in biological pathways related to cancers, neurological function, cell signalling and transcription regulation. Next, linear mixed effects models were used to determine associations between occupational exposures with methylation at the 680 loci. Of these, more CpG sites were associated with fire-runs (108 for all and 78 for structure-fires only, q<0.05) than with fire-hours (27 for all fires and 1 for structure fires). These associations were independent of time since most recent fire, suggesting an impact of cumulative exposures.
Conclusions Overall, 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.
- occupational Health
- firefighters
- epidemiology
- longitudinal studies
Data availability statement
Data are available upon reasonable request. Data requests will be reviewed by the study’s Oversight and Planning Board to address firefighter concerns prior to determination of sharing de-identified data which may include de-identified epigenomic (DNA methylation) data. This study is not a clinical trial. Contact the corresponding author, JLB, with requests.
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Data availability statement
Data are available upon reasonable request. Data requests will be reviewed by the study’s Oversight and Planning Board to address firefighter concerns prior to determination of sharing de-identified data which may include de-identified epigenomic (DNA methylation) data. This study is not a clinical trial. Contact the corresponding author, JLB, with requests.
Footnotes
Twitter @JM_Goodrich_EHS
Contributors JLB and JMG designed the concept for this study and obtained funding. JLB, SB, SL, JG and DW were instrumental in the acquisition of data for this study. JMG conducted statistical analysis and drafted the manuscript with critical intellectual input from AMJ, MAF and JLB. JLB is the guarantor for the research described in this publication. All authors approve the final version of the manuscript and accept responsibility for the accuracy and integrity of reported results.
Funding This research was supported by the National Institute of Environmental Health Sciences (NIEHS), specifically by supplements to the P30 Centers at the University of Arizona (grant no. P30 ES006694) and the University of Michigan (grant no. P30 ES017885). The US Federal Emergency Management Agency (FEMA) also supported this work (grant no. EMW-2014-FP-00200).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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