大型队列流行病学研究已证明地下矿工职业性氡暴露与肺癌风险之间的因果关系。然而，氡暴露对肺组织造成不利影响的机制仍不清楚。 DNA 甲基化等表观遗传改变可能为长期氡气暴露引起的分子水平相互作用提供新的见解。我们使用 Illumina Infinium 人类甲基化 850 K BeadChip 来检测和比较地下矿工外周血样本中的全基因组 DNA 甲基化谱（n = 14）和地上工人（n = 9）。地下工作场所的氡平均浓度显着高于地上场所（1,198 Bq·m-3 vs 58 Bq·m-3，p < 0.001）。当 |Δβ| 时，共鉴定出对应 104 个枢纽基因的 191 个差异甲基化位置（DMP）。 ≥ 0.1 且 p < 0.05，有 107 个高甲基化位点和 84 个低甲基化位点。 GO和KEGG分析显示，地下矿工和地上工人之间的差异甲基化基因在涉及神经递质调节、免疫调节作用和细胞粘附能力的通路/网络中显着富集。此外，通过焦磷酸测序验证了选定基因 FERMT1、ALCAM、HLA-DPA1、PON1 和 OR2L13 的甲基化变化，这可能在氡诱导的这些生物过程中发挥重要作用。综上所述，暴露于氡的地下矿工的 DNA 甲基化模式与地上工人不同。这种与长期接触氡气相关的基因组 DNA 甲基化谱异常值得在神经和免疫系统调节以及未来细胞粘附能力方面进行研究。© 作者 2023。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

A causal relationship between occupational radon exposure in underground miners and lung cancer risk has been demonstrated through large cohort epidemiological studies. However, the mechanisms by which radon exposure causes adverse effects on lung tissue remain unclear. Epigenetic alterations such as DNA methylation may provide new insights into interactions at molecular levels induced by prolonged radon exposure.We used the Illumina Infinium Human Methylation 850 K BeadChip to detect and compare genome-wide DNA methylation profiles in peripheral blood samples from underground miners (n = 14) and aboveground workers (n = 9).The average concentration of radon in underground workplaces was significantly higher than that of aboveground places (1,198 Bq·m-3 vs 58 Bq·m-3, p < 0.001). A total of 191 differentially methylated positions (DMPs) corresponding to 104 hub genes were identified when |Δβ| ≥ 0.1 and p < 0.05, with 107 hypermethylated sites and 84 hypomethylated sites. GO and KEGG analysis revealed that differentially methylated genes between underground miners and aboveground workers were prominently enriched in pathways/networks involved in neurotransmitter regulation, immunomodulatory effects and cell adhesion ability. Furthermore, methylation changes of selected genes FERMT1, ALCAM, HLA-DPA1, PON1 and OR2L13 were validated by pyrosequencing, which may play vital roles in these biological processes induced by radon.In summary, the DNA methylation pattern of the underground miners exposed to radon was distinct from that of the aboveground workers. Such abnormalities in the genomic DNA methylation profile associated with prolonged radon exposure are worth studying in terms of neuro- and immune-system regulation, as well as cell adhesion ability in the future.© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.