Furlong Melissa A, Liu Tuo, Jung Alesia, Beitel Shawn, Hughes Jeff, Krause Randy, Graber Judith M, Calkins Miriam M, Calafat Antonia M, Botelho Julianne C, Huentelman Matthew, Gulotta John, Goodrich Jaclyn M, Burgess Jefferey L
University of Arizona, Mel and Enid Zuckerman College of Public Health, Department of Community, Environment, and Policy, USA.
University of Arizona, Mel and Enid Zuckerman College of Public Health, Department of Community, Environment, and Policy, USA.
Environ Res. 2025 Aug 15;279(Pt 2):121766. doi: 10.1016/j.envres.2025.121766. Epub 2025 May 9.
The occupation of firefighting is classified as a Group 1 carcinogen. Increased cancer risk among firefighters may be partly attributable to increased occupational exposure to a range of chemicals, including per- and polyfluoroalkyl substances (PFAS). Some PFAS are known and suspect human carcinogens. Investigating epigenetic response to these PFAS exposures in firefighters may help to identify biological pathways of specific cancers, and previously unidentified health outcomes that are associated with PFAS. We therefore investigated the associations of serum PFAS concentrations with miRNA expression in firefighters. Serum samples collected from 303 firefighters from 6 sites across the USA were analyzed for 9 PFAS along with miRNA expression. Covariate-adjusted linear regression was used to estimate associations between log PFAS and miRNA expression, with false discovery rate (FDR) set to 0.05 for significance, and an exploratory cutoff of FDR q < 0.20. Gene set enrichment analysis (GSEA) was performed using miRTarBase's miRWalk pathways. Age, race-ethnicity, BMI, fire department, and sex were controlled for in all models. At FDR<0.05, the linear isomer of perfluorooctane sulfonic acid (PFOS) was inversely associated with miR-128-1-5p expression (Beta = -0.146, 95 % CI -0.216, -0.076). At a relaxed FDR of 0.20, we observed inverse associations for the sum of branched isomers of PFOS (Sm-PFOS) with 5 miRNAs (let-7d-5p, let-7a-5p, miR-423-5p, let-7b-5p, miR-629-5p). Several pathways were enriched for multiple PFAS, including those correlated with certain cancers, blood diseases, thyroid disorders, autoimmune disorders, and neurological outcomes. Some PFAS in firefighters were found to be associated with alteration of miRNA consistent with increased risk for a range of chronic diseases.
消防员职业被归类为第1组致癌物。消防员患癌风险增加可能部分归因于其职业中接触多种化学物质，包括全氟和多氟烷基物质（PFAS）。一些PFAS是已知的以及疑似的人类致癌物。研究消防员对这些PFAS暴露的表观遗传反应可能有助于识别特定癌症的生物学途径，以及与PFAS相关的先前未被识别的健康结果。因此，我们研究了消防员血清PFAS浓度与miRNA表达之间的关联。收集了来自美国6个地点的303名消防员的血清样本，分析了9种PFAS以及miRNA表达情况。采用协变量调整线性回归来估计log PFAS与miRNA表达之间的关联，将错误发现率（FDR）设定为0.05以确定显著性，探索性临界值为FDR q < 0.20。使用miRTarBase的miRWalk通路进行基因集富集分析（GSEA）。在所有模型中均对年龄、种族、BMI、消防部门和性别进行了控制。在FDR < 0.05时，全氟辛烷磺酸（PFOS）的线性异构体与miR - 128 - 1 - 5p表达呈负相关（β = -0.146，95% CI -0.216，-0.076）。在放宽的FDR为0.20时，我们观察到PFOS支链异构体总和（Sm - PFOS）与5种miRNA（let - 7d - 5p、let - 7a - 5p、miR - 423 - 5p、let - 7b - 5p、miR - 629 - 5p）呈负相关。多种PFAS富集了多个通路，包括与某些癌症、血液疾病、甲状腺疾病、自身免疫性疾病和神经学结果相关的通路。研究发现，消防员体内的一些PFAS与miRNA改变有关，这与一系列慢性疾病风险增加相一致。
