Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters

Epigenomics. 2021 Oct;13(20):1619-1636. doi: 10.2217/epi-2021-0225. Epub 2021 Oct 21.


Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

Keywords: environmental exposures; epigenetic age; epigenomics; firefighter; occupational exposures; per- and polyfluoroalkyl substances.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers
  • Blood Cells / drug effects
  • Blood Cells / metabolism
  • DNA Methylation* / drug effects
  • Disease Susceptibility / epidemiology
  • Disease Susceptibility / etiology
  • Epigenesis, Genetic* / drug effects
  • Female
  • Firefighters*
  • Hazardous Substances / adverse effects*
  • Health Impact Assessment
  • Humans
  • Male
  • Occupational Exposure / adverse effects*
  • Public Health Surveillance
  • Risk Assessment


  • Biomarkers
  • Hazardous Substances