DNA methylome profiling in occupational radon exposure miners using an Illumina Infinium Methylation EPIC BeadChip.

Abstract

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 850K 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 (1,198Bq·m-3 vs 58Bq·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.