Molecular Epidemiology of Uranium Exposure: Omics Approaches in Cancer Research
DOI:
https://doi.org/10.70749/ijbr.v2i1.2286Keywords:
Uranium exposure, molecular epidemiology, omics technologies, cancer biomarkers, environmental carcinogenesis, toxicogenomics, radiotoxicology.Abstract
Uranium represents both a toxic and occupational and an environmental risk factor due to its nephrotoxicity and role as a radiological alpha emitter. However, the positive correlation between total exposure to uranium and its progeny like radon progeny and the development of lung cancer in miners has been proven. Molecular epidemiology has made important strides in determining the consequences of exposure to this toxic substance through the employment of high-throughput omics analyses. Genomic studies of the exposure have made important strides in the determination of the high frequency of somatic mutations in the genes p53 and other oncogenes. This has been coupled with the determination of transcriptomal and epigenetic dysfunctions involving the DNA repair pathways. Global DNA hypomethylation together with the transcriptional hypermethylation of tumor genes like RASSF1A and CDKN2A has also been determined. MicroRNAs like miR-21 miR-34A and miR-155 have been identified. Moreover, metabolomics analyses have shown the involvement of altered lipid metabolism, amino acid turnover, and markers of oxidative stress. On the other hand, integrated analyses of multiple omics sources establish the connections between the molecular patterns and apoptosis, mitochondrial dysfunction, as well as changes in energy metabolism. Biomarkers of genotoxicity, such as elevated numbers of micronuclei and chromosomal aberrations, correlate to cumulative exposure and elevated cancer risk. In fact, the available human studies remain challenged in their limited sample size, lack of standardized exposure estimation, as well as the effect of additional exposure sources. Nonetheless, molecular epidemiology based on multiple omics analyses has unprecedented potential for improving risk assessment and the development of related preventive measures.
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