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

Goodrich, Jaclyn M.; Calkins, Miriam; Caban‐Martinez, Alberto J.; Stueckle, Todd A.; Grant, Casey C.; Calafat, Antònia M.; Nematollahi, Amy; Jung, Alesia M.; Graber, Judith M.; Jenkins, Timothy; Slitt, Angela L.; Dewald, Alisa L; Botelho, Julianne Cook; Beitel, Shawn; Littau, Sally R.; Gulotta, John; Wallentine, Darin; Hughes, Jeffery P.; Popp, Charles; Burgess, Jefferey L.

doi:10.2217/epi-2021-0225

Cited by 27 publications

(49 citation statements)

References 136 publications

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“…We also evaluated associations between exposures to perfluoroalkyl and polyfluoroalkyl substances (PFAS), one of the many chemical classes to which firefighters can be occupationally exposed, with DNA methylation among structural firefighters. We reported statistically significant associations between several PFAS with accelerated epigenetic age and altered DNA methylation at cancer-function and immune-function related genes 15. However, these previous studies were limited by lack of access to the baseline pre-firefighting epigenetic profiles.…”

Section: Introductionmentioning

confidence: 81%

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Repeat measures of DNA methylation in an inception cohort of firefighters

et al. 2022

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ObjectivesFirefighters face exposures associated with adverse health outcomes including risk for multiple cancers. DNA methylation, one type of epigenetic regulation, provides a potential mechanism linking occupational hazards to adverse health outcomes. We hypothesised that DNA methylation profiles would change in firefighters after starting their service and that these patterns would be associated with occupational exposures (cumulative fire-hours and fire-runs).MethodsWe profiled DNA methylation with the Infinium MethylationEPIC in blood leucocytes at two time points in non-smoking new recruits: prior to live fire training and 20–37 months later. Linear mixed effects models adjusted for potential confounders were used to identify differentially methylated CpG sites over time using data from 50 individuals passing all quality control.ResultsWe report 680 CpG sites with altered methylation (q value <0.05) including 60 with at least a 5% methylation difference at follow-up. Genes with differentially methylated CpG sites were enriched in biological pathways related to cancers, neurological function, cell signalling and transcription regulation. Next, linear mixed effects models were used to determine associations between occupational exposures with methylation at the 680 loci. Of these, more CpG sites were associated with fire-runs (108 for all and 78 for structure-fires only, q<0.05) than with fire-hours (27 for all fires and 1 for structure fires). These associations were independent of time since most recent fire, suggesting an impact of cumulative exposures.ConclusionsOverall, this study provides evidence that DNA methylation may be altered by fireground exposures, and the impact of this change on disease development should be evaluated.

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Section: Introductionmentioning

confidence: 81%

“…We reported statistically significant associations between several PFAS with accelerated epigenetic age and altered DNA methylation at cancer-function and immune-function related genes. 15 However, these previous studies were limited by lack of access to the baseline pre-firefighting epigenetic profiles.…”

Section: Introductionmentioning

confidence: 99%

Repeat measures of DNA methylation in an inception cohort of firefighters

et al. 2022

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“…Within the broad class of PFAS, there are numerous chemicals, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluorobutanoic acid (PFBA), perfluorohexane sulfonate (PFHxS), and “alternatives” such as GenX [ 92 – 94 ]. PFAS are known to accumulate within the body and lead to a variety of outcomes, including immunosuppression, reduced vaccine response, and epigenetic changes [ 95 , 96 ••]. Recent research has also shown associations between PFAS exposure and COVID-19 severity and mortality [ 97 ••, 98 ].…”

Section: Epigenetic Perturbations Of Immune Pathways By Environmental...mentioning

confidence: 99%

“…It is plausible that some of the immunomodulatory effects associated with PFAS may be under epigenetic regulation. In a 2021 study of firefighters, exposures to PFOA, PFOS, PFNA, PFDA, and other PFAS were associated with changes in DNA methylation for a number of genes associated with immune function [ 96 ••]. In particular, PFNA was associated with differential methylation of the Schlafen family member 12 ( SLFN12 ) and IL-32 genes that are upregulated during viral infection and T cell activation [ 111 , 112 ], while PFDA was associated with differential methylation of dual specificity phosphatase 19 ( DUSP19 ) and glycerol-3-phosphate dehydrogenase 2 ( GPD2 ), two genes involved in regulating inflammatory response [ 96 ••, 113 , 114 ].…”

Section: Epigenetic Perturbations Of Immune Pathways By Environmental...mentioning

confidence: 99%

“…In a 2021 study of firefighters, exposures to PFOA, PFOS, PFNA, PFDA, and other PFAS were associated with changes in DNA methylation for a number of genes associated with immune function [ 96 ••]. In particular, PFNA was associated with differential methylation of the Schlafen family member 12 ( SLFN12 ) and IL-32 genes that are upregulated during viral infection and T cell activation [ 111 , 112 ], while PFDA was associated with differential methylation of dual specificity phosphatase 19 ( DUSP19 ) and glycerol-3-phosphate dehydrogenase 2 ( GPD2 ), two genes involved in regulating inflammatory response [ 96 ••, 113 , 114 ]. Other research has shown hypermethylation following PFOS exposures of the genes ring finger protein 39 ( RNF39 ) and major histocompatibility complex, class II, DQ beta 1 ( HLA-DQB1 ), both associated with autoimmune conditions [ 115 , 116 ].…”

Section: Epigenetic Perturbations Of Immune Pathways By Environmental...mentioning

confidence: 99%

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Epigenetics at the Intersection of COVID-19 Risk and Environmental Chemical Exposures

Bulka

Enggasser

Fry

2022

Curr Envir Health Rpt

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Purpose of Review Several environmental contaminants have been implicated as contributors to COVID-19 susceptibility and severity. Immunomodulation and epigenetic regulation have been hypothesized as mediators of this relationship, but the precise underlying molecular mechanisms are not well-characterized. This review examines the evidence for epigenetic modification at the intersection of COVID-19 and environmental chemical exposures. Recent Findings Numerous environmental contaminants including air pollutants, toxic metal(loid)s, per- and polyfluorinated substances, and endocrine disrupting chemicals are hypothesized to increase susceptibility to the SARS-CoV-2 virus and the risk of severe COVID-19, but few studies currently exist. Drawing on evidence that many environmental chemicals alter the epigenetic regulation of key immunity genes and pathways, we discuss how exposures likely perturb host antiviral responses. Specific mechanisms vary by contaminant but include general immunomodulation as well as regulation of viral entry and recognition, inflammation, and immunologic memory pathways, among others. Summary Associations between environmental contaminants and COVID-19 are likely mediated, in part, by epigenetic regulation of key immune pathways involved in the host response to SARS-CoV-2.

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Serum per‐ and polyfluoroalkyl substance concentrations in four municipal US fire departments

Burgess

Fisher

Nematollahi

et al. 2022

American J Industrial Med

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Background Firefighters have occupational and environmental exposures to per‐ and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. Methods Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A–D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. Results In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A–C, sum of branched perfluoromethylheptane sulfonate isomers (Sm‐PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n‐PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n‐PFOA) was elevated in Departments B–D, and perfluorononanoate (PFNA) was elevated in Departments B–D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2‐(N‐methyl‐perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B–D. In female firefighters compared with NHANES, PFHxS and Sm‐PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. Conclusions Serum PFHxS, Sm‐PFOS, n‐PFOS, n‐PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.

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

Cited by 27 publications

References 136 publications

Repeat measures of DNA methylation in an inception cohort of firefighters

Repeat measures of DNA methylation in an inception cohort of firefighters

Epigenetics at the Intersection of COVID-19 Risk and Environmental Chemical Exposures

Serum per‐ and polyfluoroalkyl substance concentrations in four municipal US fire departments

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