Abstract Firefighters are exposed to high levels of toxic chemicals when fighting fires, and previous studies have established these men and woman have a significantly elevated risk for various cancers. Improved risk management for firefighters requires identification of biomarkers indicative of physiological response. Micro-RNAs (miRNA) have emerged as a promising noninvasive prognostic and diagnostic biomarkers for various diseases. Here we isolated miRNA from the urine of a large dataset of firefighters, collected pre- and post-fire exposure as well as from healthy non-firefighter controls. miRNA was analyzed by microarray using the Affymetrix GeneCHIP miRNA 4.0 array. Analysis revealed 23 human miRNAs were significantly up-regulated and 25 significantly down-regulated in firefighters compared to control samples (analysis 1). Gene targets of these miRNAs were analyzed using the Online Database for Annotation, Visualization, and Integrated Discovery (DAVID) and found to cluster in several pathways and disease associations with smoking, cancer, and inflammatory diseases. Furthermore, we performed a longitudinal analysis of samples from firefighters that provided a sample prior to a fire exposure and immediately after a fire (analysis 2). This analysis found 20 miRNAs that were significantly up-regulated post fire exposure. Of these, 5 were also up-regulated in firefighters vs control samples (hsa-miR-1268b, hsa-miR-4433b-3p, hsa-miR-4253, hsa-miR-6824-5p, and hsa-miR-3188). Again, analysis of gene targets of these miRNAs found association of mostly the same pathways and disease processes found in analysis 1. These findings are consistent with epidemiological evidence for increased risks associated with firefighting and offer a proof of concept and framework for the use of miRNA in urine as biomarkers for health risk assessment associated with firefighting.
Sachs et al. (Wed,) studied this question.