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Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case–control study

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Abstract

The clarification of possible exposure sources of multiple metals to identify associations between metal doses and urothelial carcinoma (UC) risk is currently limited in the literature. We sought to identify the exposure sources of 10 metals (Vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, cadmium, and lead) using principal component analysis (PCA) and then linked various principal component (PC) scores with environmental characteristics, including smoking-related indices, PM2.5, and distance to the nearest bus station. In addition, urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) and DNA hypomethylation markers (5-methyl-2’-deoxycytidine levels; %5-MedC) were investigated in combination with UC risks. We conducted this hospital-based case control study in 359 UC patients with histologically confirmed disease and 718 controls. All data were collected from face-to-face interviews and medical records. Approximately 6 mL blood was collected from participants for analysis of multiple heavy metal and DNA methylation in leukocyte DNA. Further, a 20 mL urine sample was collected to measure urinary cotinine and 8-OHdG levels. In addition, average values for PM2.5 for individual resident were calculated using the hybrid kriging/land-use regression model. In UC patients, significantly higher cobalt, nickel, copper, arsenic, and cadmium (μg/L) levels were observed in blood when compared with controls. Three PCs with eigenvalues > 1 accounted for 24.3, 15.8, and 10.7% of UC patients, and 26.9, 16.7, and 11.1% of controls, respectively. Environmental metal sources in major clusters were potentially associated with industrial activities and traffic emissions (PC1), smoking (PC2), and food consumption, including vitamin supplements (PC3). Multiple metal doses were linked with incremental urinary 8-OHdG and DNA hypomethylation biomarkers. For individuals with high PC1 and PC2 scores, both displayed an approximate 1.2-fold risk for UC with DNA hypomethylation.

In conclusion, we provide a foundation for health education and risk communication strategies to limit metal exposure in environment, so that UC risks can be improved potentially.

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Data Availability Statement

Data used and analyzed in the manuscript will be made available upon request.

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Acknowledgements

This study was supported by grants from the National Science Council (NSC 101-2314-B-039-025-MY3 and MOST 108-2221-E-039-009-MY3) and China Medical University and Hospital (DMR-105-049, CMU106-S-20, CMU107-S-06, and CMU108-MF-94). The funders did not participate in the study design, data collection and analysis, publication decision, or manuscript preparation.

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Authors and Affiliations

  1. Department of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City, 406040, Taiwan

    Chi-Jung Chung & Hui-Tsung Hsu

  2. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

    Chi-Jung Chung

  3. Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan

    Hui-Ling Lee

  4. Department of Urology, China Medical University and Hospital, Taichung, Taiwan

    Chao-Hsiang Chang

  5. Department of Geomatics, National Cheng Kung University, Tainan, Taiwan

    Chih-Da Wu

  6. Adjunct Assistant Research Fellow, National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan

    Chih-Da Wu

  7. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan

    Chiu-Shong Liu

  8. Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

    Mu-Chi Chung

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Contributions

MCC, HTH, HLL, CHC, CDW, CSL, and CJC conceived and designed experiments, HTH and CJC conducted experiments, HTH and CJC analyzed data, MCC, HTH, HLL, CHC, CDW, CSL, and CJC contributed material, and HTH and CJC drafted manuscript.

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Correspondence to Hui-Tsung Hsu.

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Chung, CJ., Lee, HL., Chang, CH. et al. Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case–control study. Environ Geochem Health 45, 5401–5414 (2023). https://doi.org/10.1007/s10653-023-01481-3

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