Abstract
The relationship between heavy metal exposure and human health has been investigated mostly for individual metals, failing to consider their potential interactions. In this study, we assessed the joint effects of multiple metals using generalized weighted quantile sum (WQS) regression on the risk of urothelial carcinoma (UC). Also, we performed mediation analysis to evaluate the mediator %5-MedC in DNA involved in the mechanism of urothelial carcinogenesis. We conducted a hospital-based case–control study of 355 UC patients and 710 controls, where diagnosis of UC was histologically confirmed. All data were collected from face-to-face interviews and medical records. Also, we measured six metals and 8-OHdG in urine samples along with %5-MedC in peripheral blood. Ni and Pb levels increased with UC risk in single-pollutant analysis using traditional logistic regression, and similar results were obtained in multi-pollutant analysis, where all metals analyzed were considered. In WQS analysis, the weights of Ni (27%), Pb (20%), Cr (18%), and Co (16%) predominated in the metal mixture index. WQS score and UC risk showed odds ratios of 1.65 (95%CI: 1.26, 2.15) and 1.43 (95%CI: 1.00, 2.05) for a linear and non-linear relationship, respectively. Finally, we did not observe a natural indirect effect of %5-MedC in DNA; however, a marginal effect of WQS score and natural direct effect were still found after considering a natural indirect effect. In conclusion, positive associations between WQS scores and increased risk of UC were observed. Interactions of multiple metals should be considered in assessing human health risk.
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Acknowledgements
This study was supported by grants from the National Science Council (NSC101-2314-B-039-025-MY3) and China Medical University Hospital (DMR-105-049). The funders did not participate in the study design, data collection and analysis, publication decision, or manuscript preparation.
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Conceived and designed experiments: HTH, HLL, HHC, CHC, CSL, PJH, HC, CSL, MCC and CJC. Conducted experiments: HLL, HHC, and CJC. Analyzed data: HTH and CJC. Contributed material: HTH, HLL, CHC, CSL, PJH, HC, CSL, MCC and CJC. Drafted manuscript: HTH, MCC and CJC.
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Hsu, HT., Lee, HL., Cheng, HH. et al. Relationships of multiple metals exposure, global DNA methylation, and urothelial carcinoma in central Taiwan. Arch Toxicol 96, 1893–1903 (2022). https://doi.org/10.1007/s00204-022-03260-y
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DOI: https://doi.org/10.1007/s00204-022-03260-y