Serum biomarkers associated with health impacts of high residential radon exposure: a metabolomic pilot study

Long-term epidemiological evidence suggests that populations exposed to high natural radiation levels for extended periods may have an increased risk of cancer and other diseases. However, research on health effects in high-radon areas, particularly regarding disease-related biomarkers, remains limited. This study aimed to investigate serum metabolic biomarkers associated with diseases in individuals from areas with high radon exposure. Metabolic profiling was performed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry on 30 healthy participants comprising 15 individuals from a low-residential radon exposure group and 15 from a high-residential radon exposure group. Multivariate analysis, receiver operating characteristic (ROC) curve analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied. Partial least-squares discriminant analysis revealed significant differences (P < 0.05) between the two groups, identifying 92 metabolites. ROC analysis (AUC ≥ 0.85) highlighted 12 key candidates associated with high radon exposure. KEGG pathway analysis linked D-sphingosine to lung cancer development and 3-methylhistidine to kidney disease, early preeclampsia, and Alzheimer's disease. These findings suggest that D-sphingosine and 3-methylhistidine are promising serum biomarkers for identifying high-risk individuals with prolonged radon exposure and contribute to the identification of novel biomarkers in future studies on high-radon exposure areas.