LT

Introduction Firefighters face regular exposure to known and probable human carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), benzene, and formaldehyde, leading to an increased risk of various cancers compared to the general population. Hispanic and black firefighters are at increased risk of additional cancers not elevated in non-Hispanic white firefighters, yet biological pathways underlying these differences are unknown. Objectives The study objectives were to evaluate differences in the urinary metabolome between Hispanic and non-Hispanic firefighters, pre-and post-fireground exposure. Methods To investigate the metabolic patterns, we employed a comprehensive metabolomics pipeline that leveraged liquid chromatography coupled with high-resolution mass spectrometry. We applied linear mixed effects regression to identify the differential metabolites at an FDR < 0.05 among 19 Hispanic and 81 non-Hispanic firefighters. We also performed overrepresentation analysis using Mummichog to identify enriched pathways at FDR < 0.05. Results Out of 175 features in HILIC(−) mode and 1847 features in RP(+) mode, we found 26 and 276 differential urinary features, respectively, when comparing Hispanic and non-Hispanic firefighters. We noted pathway enrichment in tryptophan and galactose metabolism. However, post-exposure, we did not observe differences in the metabolomic response by ethnicity despite differing fireground exposures. Conclusion Dysregulation in the tryptophan and galactose pathway is an important contributor to cancer risks and may explain the increased cancer risk among Hispanic firefighters. Supplementary Information The online version contains supplementary material available at 10.1007/s11306-024-02198-9.

Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers.