Circulating metabolomic and chemical exposomics signatures as potential biomarkers for long-term radon exposure

Radon is a radioactive gas and a lung carcinogen, yet lacks established blood biomarkers for long-term exposure. We aimed to identify circulating metabolomic and exposomics signatures correlated with reconstructed radon-222 exposure. Metabolites and chemical exposomes were profiled using liquid and gas chromatography-high-resolution mass spectrometry from plasma (n = 80). Batch effects were corrected using ComBat, and network and pathway analyses were performed using xMWAS and MetaboAnalyst, respectively. A total of 124 metabolites were correlated with radon, including 41 positive correlations. The strongest positive and negative associations involved unidentified features. Network analysis identified six communities, five of which were directly related to radon. Fatty acyls were the most represented class, followed by benzene derivatives and hydroxy acids and derivatives. Pathway analysis showed enrichment in linoleate, fatty acid, and amino acid metabolism. Our findings demonstrate that integrating metabolomic and chemical exposomes may help identify sensitive biomarkers for radon exposure. We recommend further studies to investigate these pathways in greater mechanistic detail to understand the health effects of radon.