Omichessan Hanane, Dragic Dzevka, Perduca Vittorio, Truong Thérèse, Polidoro Silvia, Kvaskoff Marina, Cano-Sancho German, Antignac Jean-Philippe, Baglietto Laura, Mancini Francesca Romana, Severi Gianluca
Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France.
Département de Médecine Sociale et Préventive, Faculté de Médecine, Université Laval, Québec, QC, Canada.
Front Public Health. 2025 Jul 28;13:1621495. doi: 10.3389/fpubh.2025.1621495. eCollection 2025.
Perfluorooctanoic 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.
We 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.
We found 64 CpG sites with significant hypomethylation or hypermethylation associated with increased levels of PFOA or PFOS (-value < 0.05). The strongest association was found between PFOA serum levels and decreased DNAm at cg06874740 (-value = 2.2×10) and between PFOS serum levels and decreased DNAm at cg02793158 (-value = 9.3×10). Gene-set enrichment analyses using all CpG sites associated with PFOA or PFOS with an unadjusted -value <0.01, identified 20 KEGG pathways for each of these compounds.
PFAS 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.
全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）属于全氟和多氟烷基物质（PFAS）组中的众多化学物质，它们普遍存在于各种消费品和工业产品中。这些化学物质因其持久性、在生物系统中积累的能力以及对人类健康的不良影响而被人们所认识。先前的研究主要集中在全球甲基化模式上，表明PFAS对人类健康的某些影响可能与DNA甲基化（DNAm）的改变有关。我们研究的目的是评估血清中PFOS和PFOA水平与外周血DNA的CpG位点特异性甲基化之间的关系。
我们在E3N队列（一项针对法国女性的前瞻性研究）中进行了一项关于乳腺癌的病例对照研究，其中我们使用Illumina Infinium MethylationEPIC BeadChip对166对病例对照进行了超过850,000个CpG位点的DNAm测量。通过液相色谱-串联质谱法测量血清中PFOS和PFOA的水平。
我们发现64个CpG位点存在与PFOA或PFOS水平升高相关的显著低甲基化或高甲基化（P值<0.05）。在PFOA血清水平与cg06874740处DNAm降低之间（P值=2.2×10）以及PFOS血清水平与cg02793158处DNAm降低之间（P值=9.3×10）发现了最强的关联。使用所有与PFOA或PFOS相关且未调整的P值<0.01的CpG位点进行基因集富集分析，为每种化合物确定了20条KEGG通路。
PFAS暴露可能与甲基化组的大量广泛变化有关，这些变化可能与这些污染物对健康的影响有关。我们的研究结果表明，PFOA和PFOS的生物学和健康影响可能比以前认为的更加复杂多样，这加强了制定旨在监管这类内分泌干扰化学物质的政策的必要性。
