Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Department of Community, Environment, and Policy, University of Arizona Mel and Enid Zuckerman College of Public Health, Tucson, Arizona, USA.
Occup Environ Med. 2022 Oct;79(10):656-663. doi: 10.1136/oemed-2021-108153. Epub 2022 Mar 24.
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).
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.
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.
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.
消防员面临与不良健康结果相关的暴露，包括多种癌症的风险。DNA 甲基化是一种表观遗传调控方式，为职业危害与不良健康结果之间的联系提供了潜在机制。我们假设，消防员开始服役后，其 DNA 甲基化谱会发生变化，并且这些模式与职业暴露（累积火灾小时数和火灾出动次数）有关。
我们在两次时间点使用 Infinium MethylationEPIC 在非吸烟新兵的血液白细胞中进行 DNA 甲基化谱分析：在进行实火训练之前和 20-37 个月之后。使用通过所有质量控制的 50 名个体的数据，使用线性混合效应模型调整潜在混杂因素，以确定随时间变化的差异甲基化 CpG 位点。
我们报告了 680 个甲基化改变的 CpG 位点（q 值<0.05），其中 60 个在随访时至少有 5%的甲基化差异。差异甲基化 CpG 位点的基因在与癌症、神经功能、细胞信号和转录调节相关的生物学途径中富集。接下来，使用线性混合效应模型确定职业暴露与 680 个基因座的甲基化之间的关联。在这些基因座中，与火灾出动次数（所有火灾 108 个，仅结构火灾 78 个，q<0.05）相关的 CpG 位点多于与火灾小时数（所有火灾 27 个，仅结构火灾 1 个）相关的 CpG 位点。这些关联独立于最近一次火灾后的时间，表明累积暴露的影响。
总的来说，这项研究提供了证据表明，DNA 甲基化可能会因火灾现场暴露而改变，并且应该评估这种变化对疾病发展的影响。
