Associations of Serum Per- and Polyfluoroalkyl Substances (PFAS) With Epigenetic Age and DNA Methylation in US Airport Firefighters

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in a variety of consumer and industrial applications for their water- and oil-resistant properties. Firefighters can be exposed to PFAS as part of their job through gear, aqueous film-forming foams (AFFFs) used to extinguish aircraft and liquid fuel fires, along with exposure through other combustible materials during fire suppression activities. PFAS exposure has been linked to a variety of health conditions including cancer, obesity, reproductive issues, and immunosuppression. Epigenetic modifications may be one mechanism underlying PFAS toxicity. In this study, we used epigenetic indicators to assess association of PFAS serum concentrations with (1) epigenetic aging and (2) DNA methylation at loci within genes related to immune function. Blood leukocyte DNA methylation was quantified via the Infinium EPIC array from 184 participants in the Fire Fighter Cancer Cohort Study involved in aircraft rescue and firefighting, and serum PFAS was measured via on-line solid phase extraction liquid chromatography isotope dilution tandem mass spectrometry. We observed inverse associations between PFAS concentrations and epigenetic clocks including between serum linear perfluorooctanoic acid (n-PFOA) with four epigenetic clocks (p < 0.05); however, most did not remain significant in sensitivity analyses. Associations (q < 0.1) were observed between perfluorodecanoic acid, n-PFOA, sum of branched perfluorooctane sulfonic acid isomers and differential methylation of specific loci within 34 immune-related genes. Further research can help to better understand the functional impacts of the observed differential methylation on immune health.