Per- and Polyfluoroalkyl Substances, Epigenetic Age and DNA Methylation: A Cross-Sectional Study of Firefighters

Abstract

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.

Lay abstract

Per- and poly-fluoroalkyl substances (PFASs) are a group of toxic chemicals that populations around the world are widely exposed to through contaminated water and consumer products. Firefighters can also be exposed to PFASs from occupational practices. Epigenetic modifications, including DNA methylation, regulate gene expression. It can be modified by environmental exposures such as PFASs, which contribute to the development of diseases including cancer. We measured the concentrations of nine PFASs in samples from firefighters and profiled DNA methylation across the genome. Three PFASs were linked with accelerated epigenetic age, a marker associated with many diseases. Four PFASs were associated with altered DNA methylation levels at specific genes. These results may indicate how PFASs are harmful to health and merit further exploration.

Keywords::

• environmental exposures
• epigenetic age
• epigenomics
• firefighter
• occupational exposures
• per- and polyfluoroalkyl substances

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0225

Author contributions

JL Burgess, MM Calkins, AJ Caban-Martinez, C Grant and JM Goodrich designed the research study; JL Burgess, AJ Caban-Martinez and MM Calkins obtained funding and designed protocols to develop the cohorts with consultation from C Grant, JM Goodrich, J Gulotta, D Wallentine, J Hughes and C Popp; J Gulotta, D Wallentine, J Hughes and C Popp recruited subjects and collected data; AM Jung, A Nematollahi, S Beitel, S Littau, MM Calkins and JL Burgess managed data and samples; AM Calafat and J Cook Botelho conducted exposure assessment; JM Goodrich, T Jenkins and A Dewald conducted the DNA methylation analysis; JM Goodrich conducted statistical analysis and led manuscript drafting with critical input from all coauthors and JM Graber, T Stueckle, AL Slitt, AM Jung and A Nematollahi provided interpretation of results and initial manuscript drafting. All authors contributed to the writing and/or editing of the manuscript and approve this final submission.

Acknowledgments

The authors would like to thank the firefighter participants for graciously volunteering their time and samples to be in the study. The authors would also like to thank the partnering fire departments and their locals for their contribution to this research and K Kato, K Hubbard, J Eng and R Hatchett for the quantification of PFASs concentrations. The University of Michigan Advanced Genomics Core and the University of Utah DNA Sequencing and Genomics Core Facility completed the EPIC analyses.

Financial & competing interests disclosure

This research was supported by the National Institute of Environmental Health Sciences (NIEHS), specifically by supplements to the P30 Centers at the University of Arizona (grant no. P30 ES006694) and the University of Michigan (grant no. P30 ES017885). The US Federal Emergency Management Agency (FEMA) supported this work (grant nos. EMW-2014-FP-00200, EMW-2015-FP-00213, and EMW-2018-FP-00086). The International Association of Fire Fighters (IAFF) also supported this work. The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or other funding agencies. Mention of trade names and commercial products does not constitute endorsement or recommendation for use by CDC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval from the University of Arizona IRB and the University of Miami IRB. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

Data requests will be reviewed by the Fire Fighter Cancer Cohort Study fire service Oversight and Planning Board to address firefighter concerns prior to determination of sharing de-identified data. This study is not a clinical trial.

Additional information

Funding

This research was supported by the National Institute of Environmental Health Sciences (NIEHS), specifically by supplements to the P30 Centers at the University of Arizona (grant no. P30 ES006694) and the University of Michigan (grant no. P30 ES017885). The US Federal Emergency Management Agency (FEMA) supported this work (grant nos. EMW-2014-FP-00200, EMW-2015-FP-00213, and EMW-2018-FP-00086). The International Association of Fire Fighters (IAFF) also supported this work. The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or other funding agencies. Mention of trade names and commercial products does not constitute endorsement or recommendation for use by CDC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.