Per- and Polyfluoroalkyl Substances, Epigenetic Age and DNA Methylation: A cross-sectional Study of Firefighters

Overview

Journal Epigenomics

Specialty Genetics

Date 2021 Oct 21

PMID 34670402

Citations 12

Authors

Jaclyn M Goodrich

Miriam M Calkins

Alberto J Caban-Martinez

Todd Stueckle

Casey Grant

Antonia M Calafat

Amy Nematollahi

Alesia M Jung

Judith M Graber

Timothy Jenkins

Angela L Slitt

Alisa Dewald

Julianne Cook Botelho

Shawn Beitel

Sally Littau

John Gulotta

Darin Wallentine

Jeff Hughes

Charles Popp

Jefferey L Burgess

Affiliations

Soon will be listed here.

Abstract

Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. 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. 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. PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

Citing Articles

Epigenetic Modifications Associated With Wildland-Urban Interface (WUI) Firefighting.

Goodrich J, Furlong M, Urwin D, Gabriel J, Hughes J, Jung A Environ Mol Mutagen. 2025; 66(1-2):22-33.

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Lifetime Postnatal Exposure to Perfluoroalkyl Substance Mixture and DNA Methylation at Twelve Years of Age.

Liu Y, Gairola R, Kuiper J, Papandonatos G, Kelsey K, Langevin S Environ Sci Technol Lett. 2025; 10(10):824-830.

PMID: 39831111 PMC: 11741666. DOI: 10.1021/acs.estlett.3c00410.

Associations between use of chemical hair products and epigenetic age: Findings from the Sister Study.

Chang C, OBrien K, Kresovich J, Nwanaji-Enwerem J, Xu Z, Gaston S Environ Epidemiol. 2024; 8(3):e311.

PMID: 38799263 PMC: 11115975. DOI: 10.1097/EE9.0000000000000311.

Per- and polyfluoroalkyl substances alter innate immune function: evidence and data gaps.

Phelps D, Connors A, Ferrero G, DeWitt J, Yoder J J Immunotoxicol. 2024; 21(1):2343362.

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Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk.

Quaid M, Goodrich J, Calkins M, Graber J, Urwin D, Gabriel J Environ Mol Mutagen. 2024; 65(1-2):55-66.

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References

Leettola C, Knight M, Cascio D, Hoffman S, Bowie J . Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3. BMC Struct Biol. 2014; 14:17. PMC: 4105859. DOI: 10.1186/1472-6807-14-17. View

Wright R, Schwartz J, Wright R, Bollati V, Tarantini L, Park S . Biomarkers of lead exposure and DNA methylation within retrotransposons. Environ Health Perspect. 2010; 118(6):790-5. PMC: 2898855. DOI: 10.1289/ehp.0901429. View

Yang J, Teehan D, Farioli A, Baur D, Smith D, Kales S . Sudden cardiac death among firefighters ≤45 years of age in the United States. Am J Cardiol. 2013; 112(12):1962-7. PMC: 7750027. DOI: 10.1016/j.amjcard.2013.08.029. View

Sikdar S, Joehanes R, Joubert B, Xu C, Vives-Usano M, Rezwan F . Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking. Epigenomics. 2019; 11(13):1487-1500. PMC: 6836223. DOI: 10.2217/epi-2019-0066. View

Ikegami K, Sato S, Nakamura K, Ostrowski L, Setou M . Tubulin polyglutamylation is essential for airway ciliary function through the regulation of beating asymmetry. Proc Natl Acad Sci U S A. 2010; 107(23):10490-5. PMC: 2890849. DOI: 10.1073/pnas.1002128107. View

Baylin S, Jones P . A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011; 11(10):726-34. PMC: 3307543. DOI: 10.1038/nrc3130. View

Fhu C, Ali A . Fatty Acid Synthase: An Emerging Target in Cancer. Molecules. 2020; 25(17). PMC: 7504791. DOI: 10.3390/molecules25173935. View

Boronow K, Brody J, Schaider L, Peaslee G, Havas L, Cohn B . Serum concentrations of PFASs and exposure-related behaviors in African American and non-Hispanic white women. J Expo Sci Environ Epidemiol. 2019; 29(2):206-217. PMC: 6380931. DOI: 10.1038/s41370-018-0109-y. View

Tibbles L, Woodgett J . The stress-activated protein kinase pathways. Cell Mol Life Sci. 1999; 55(10):1230-54. PMC: 11147067. DOI: 10.1007/s000180050369. View

10.

Pasello M, Giudice A, Scotlandi K . The ABC subfamily A transporters: Multifaceted players with incipient potentialities in cancer. Semin Cancer Biol. 2019; 60:57-71. DOI: 10.1016/j.semcancer.2019.10.004. View

11.

Kim S, Thapar I, Brooks B . Epigenetic changes by per- and polyfluoroalkyl substances (PFAS). Environ Pollut. 2021; 279:116929. DOI: 10.1016/j.envpol.2021.116929. View

12.

Wang C, Ni W, Yao Y, Just A, Heiss J, Wei Y . DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4. EBioMedicine. 2020; 63:103151. PMC: 7724153. DOI: 10.1016/j.ebiom.2020.103151. View

13.

Houseman E, Accomando W, Koestler D, Christensen B, Marsit C, Nelson H . DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012; 13:86. PMC: 3532182. DOI: 10.1186/1471-2105-13-86. View

14.

Williams S, BAKER B, Lee K . Formation of acute pulmonary toxicants following thermal degradation of perfluorinated polymers: evidence for a critical atmospheric reaction. Food Chem Toxicol. 1987; 25(2):177-85. DOI: 10.1016/0278-6915(87)90152-9. View

15.

Mansell G, Gorrie-Stone T, Bao Y, Kumari M, Schalkwyk L, Mill J . Guidance for DNA methylation studies: statistical insights from the Illumina EPIC array. BMC Genomics. 2019; 20(1):366. PMC: 6518823. DOI: 10.1186/s12864-019-5761-7. View

16.

Post G, Louis J, Lippincott R, Procopio N . Occurrence of perfluorinated compounds in raw water from New Jersey public drinking water systems. Environ Sci Technol. 2013; 47(23):13266-75. DOI: 10.1021/es402884x. View

17.

Jung A, Zhou J, Beitel S, Littau S, Gulotta J, Wallentine D . Longitudinal evaluation of whole blood miRNA expression in firefighters. J Expo Sci Environ Epidemiol. 2021; 31(5):900-912. PMC: 8445815. DOI: 10.1038/s41370-021-00306-8. View

18.

Barry V, Winquist A, Steenland K . Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect. 2013; 121(11-12):1313-8. PMC: 3855514. DOI: 10.1289/ehp.1306615. View

19.

Lokk K, Vooder T, Kolde R, Valk K, Vosa U, Roosipuu R . Methylation markers of early-stage non-small cell lung cancer. PLoS One. 2012; 7(6):e39813. PMC: 3387223. DOI: 10.1371/journal.pone.0039813. View

20.

Langston P, Nambu A, Jung J, Shibata M, Aksoylar H, Lei J . Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses. Nat Immunol. 2019; 20(9):1186-1195. PMC: 6707851. DOI: 10.1038/s41590-019-0453-7. View