Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral blood

BackgroundPerfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) are among numerous chemicals in the Per- and polyfluoroalkylated substances (PFAS) group, which are commonly present in various consumer and industrial products. These chemicals are recognized for their persistency, the abi...

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Main Authors: Hanane Omichessan, Dzevka Dragic, Vittorio Perduca, Thérèse Truong, Silvia Polidoro, Marina Kvaskoff, German Cano-Sancho, Jean-Philippe Antignac, Laura Baglietto, Francesca Romana Mancini, Gianluca Severi
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Public Health
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Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2025.1621495/full
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author Hanane Omichessan
Dzevka Dragic
Dzevka Dragic
Dzevka Dragic
Vittorio Perduca
Vittorio Perduca
Thérèse Truong
Silvia Polidoro
Marina Kvaskoff
German Cano-Sancho
Jean-Philippe Antignac
Laura Baglietto
Francesca Romana Mancini
Gianluca Severi
Gianluca Severi
author_facet Hanane Omichessan
Dzevka Dragic
Dzevka Dragic
Dzevka Dragic
Vittorio Perduca
Vittorio Perduca
Thérèse Truong
Silvia Polidoro
Marina Kvaskoff
German Cano-Sancho
Jean-Philippe Antignac
Laura Baglietto
Francesca Romana Mancini
Gianluca Severi
Gianluca Severi
author_sort Hanane Omichessan
collection DOAJ
description BackgroundPerfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) are among numerous chemicals in the Per- and polyfluoroalkylated substances (PFAS) group, which are commonly present in various consumer and industrial products. These chemicals are recognized for their persistency, the ability to accumulate in biological systems and their documented adverse effects on human health. Previous research, which has primarily centered on global methylation patterns, has suggested that some effects of PFAS on human health may be linked to modifications in DNA methylation (DNAm). The aim of our study was to assess the relationship between the serum levels of PFOS and PFOA and CpG site-specific methylation of DNA from peripheral blood.MethodsWe used a case–control study on breast cancer nested within the E3N cohort, a prospective study of French women, in which we measured DNAm at more than 850,000 CpG sites with the Illumina Infinium MethylationEPIC BeadChip for 166 case–control pairs. Serum levels of PFOS and PFOA were measured by liquid chromatography coupled to tandem mass spectrometry.ResultsWe found 64 CpG sites with significant hypomethylation or hypermethylation associated with increased levels of PFOA or PFOS (p-valueBonferroni < 0.05). The strongest association was found between PFOA serum levels and decreased DNAm at cg06874740 (p-valueBonferroni = 2.2×10−5) and between PFOS serum levels and decreased DNAm at cg02793158 (p-valueBonferroni = 9.3×10−5). Gene-set enrichment analyses using all CpG sites associated with PFOA or PFOS with an unadjusted p-value <0.01, identified 20 KEGG pathways for each of these compounds.ConclusionPFAS exposure may be linked to substantial and widespread changes in the methylome that may be involved in the consequences on health of these pollutants. Our findings indicate that the biological and health effects of PFOA and PFOS may be more intricate and varied than previously thought, reinforcing the need for policies aimed at regulating this class of endocrine-disrupting chemicals.
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spelling doaj-art-4fb03f25329a4c2e9bcef9d5fda6fe9f2025-08-20T03:56:50ZengFrontiers Media S.A.Frontiers in Public Health2296-25652025-07-011310.3389/fpubh.2025.16214951621495Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral bloodHanane Omichessan0Dzevka Dragic1Dzevka Dragic2Dzevka Dragic3Vittorio Perduca4Vittorio Perduca5Thérèse Truong6Silvia Polidoro7Marina Kvaskoff8German Cano-Sancho9Jean-Philippe Antignac10Laura Baglietto11Francesca Romana Mancini12Gianluca Severi13Gianluca Severi14Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, FranceUniversité Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, FranceDépartement de Médecine Sociale et Préventive, Faculté de Médecine, Université Laval, Québec, QC, CanadaCentre de Recherche sur le Cancer, Centre de Recherche du CHU de Québec - Université Laval, Axe Oncologie, Québec, QC, CanadaUniversité Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, FranceUniversité Paris Cité, CNRS, MAP5, Paris, FranceUniversité Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, FranceDepartment of Translational Medicine, University of Eastern Piedmont, Novara, ItalyUniversité Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, FranceOniris, INRAE, LABERCA, Nantes, FranceOniris, INRAE, LABERCA, Nantes, FranceDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyUniversité Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, FranceUniversité Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, FranceDepartment of Statistics, Computer Science, Applications "G. Parenti" (DISIA), University of Florence, Florence, ItalyBackgroundPerfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) are among numerous chemicals in the Per- and polyfluoroalkylated substances (PFAS) group, which are commonly present in various consumer and industrial products. These chemicals are recognized for their persistency, the ability to accumulate in biological systems and their documented adverse effects on human health. Previous research, which has primarily centered on global methylation patterns, has suggested that some effects of PFAS on human health may be linked to modifications in DNA methylation (DNAm). The aim of our study was to assess the relationship between the serum levels of PFOS and PFOA and CpG site-specific methylation of DNA from peripheral blood.MethodsWe used a case–control study on breast cancer nested within the E3N cohort, a prospective study of French women, in which we measured DNAm at more than 850,000 CpG sites with the Illumina Infinium MethylationEPIC BeadChip for 166 case–control pairs. Serum levels of PFOS and PFOA were measured by liquid chromatography coupled to tandem mass spectrometry.ResultsWe found 64 CpG sites with significant hypomethylation or hypermethylation associated with increased levels of PFOA or PFOS (p-valueBonferroni < 0.05). The strongest association was found between PFOA serum levels and decreased DNAm at cg06874740 (p-valueBonferroni = 2.2×10−5) and between PFOS serum levels and decreased DNAm at cg02793158 (p-valueBonferroni = 9.3×10−5). Gene-set enrichment analyses using all CpG sites associated with PFOA or PFOS with an unadjusted p-value <0.01, identified 20 KEGG pathways for each of these compounds.ConclusionPFAS exposure may be linked to substantial and widespread changes in the methylome that may be involved in the consequences on health of these pollutants. Our findings indicate that the biological and health effects of PFOA and PFOS may be more intricate and varied than previously thought, reinforcing the need for policies aimed at regulating this class of endocrine-disrupting chemicals.https://www.frontiersin.org/articles/10.3389/fpubh.2025.1621495/fullendocrine disrupting chemicalsenvironmental exposureDNA methylationPFOAPFOS
spellingShingle Hanane Omichessan
Dzevka Dragic
Dzevka Dragic
Dzevka Dragic
Vittorio Perduca
Vittorio Perduca
Thérèse Truong
Silvia Polidoro
Marina Kvaskoff
German Cano-Sancho
Jean-Philippe Antignac
Laura Baglietto
Francesca Romana Mancini
Gianluca Severi
Gianluca Severi
Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral blood
Frontiers in Public Health
endocrine disrupting chemicals
environmental exposure
DNA methylation
PFOA
PFOS
title Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral blood
title_full Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral blood
title_fullStr Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral blood
title_full_unstemmed Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral blood
title_short Serum levels of per- and polyfluoroalkylated substances and methylation of DNA from peripheral blood
title_sort serum levels of per and polyfluoroalkylated substances and methylation of dna from peripheral blood
topic endocrine disrupting chemicals
environmental exposure
DNA methylation
PFOA
PFOS
url https://www.frontiersin.org/articles/10.3389/fpubh.2025.1621495/full
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