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Relationships among cigarette smoking, urinary biomarkers, and urothelial carcinoma risk: a case-control study

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Abstract

Cigarette smoke is a known risk factor for urothelial carcinoma (UC). However, there is limited information about the distributions and effects of volatile organic compounds (VOCs) on smoking-related UC risk. With this hospital-based case-control study, we explored the associations between urinary levels of cotinine and VOC metabolites (acrylamide, 1,3-butadiene, and benzene) and the risk of UC. Urological examinations and pathological verifications were used to confirm the diagnoses of UC. All study participants provided smoking-related information via questionnaires and face-to-face interviews; they also provided urine samples for the measurement of VOC metabolites, cotinine, and 8-hydroxydeoxyguanosine (8-OHdG), which was used as an indicator of oxidative stress. We applied multiple logistic regression analysis to estimate the risk of UC, and we found that levels of urinary cotinine and 8-OHdG were higher in the UC group than in the control group. Furthermore, urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine-3, trans,trans-muconic acid (t,t-MA), and S-phenylmercapturic acid (SPMA), increased with increasing levels of urinary cotinine. After adjusting for potential risk factors, dose–response relationships were observed between UC risk and urinary levels of AAMA, t,t-MA, SPMA, and 8-OHdG. Participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG had risks of UC that were 3.5- to 6-fold higher than those of participants with lower levels. Future, large-scale investigations of the risks of UC should be explored, and repeated measurement of VOC metabolites should be assessed.

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Abbreviations

VOCs:

Volatile organic compounds

UC:

Urothelial carcinoma

AAMA:

N-acetyl-S-(2-carbamoylethyl)-L-cysteine

GAMA:

N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine

DHBMA:

N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine

MHBMA-3:

N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine-3

t,t-MA:

trans,trans-muconic acid

SPMA:

S-phenylmercapturic acid

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Funding

This study was supported by grants from the Ministry of Science and Technology of the ROC (MOST107-2113-M-030-003) and China Medical University Hospital (DMR-105-081). 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, China Medical University, No. 91 Hsueh-Shih Road, Taichung, 40402, Taiwan

    Chi-Jung Chung, Hui-Tsung Hsu & Guo-Wei Wu

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

    Chi-Jung Chung

  3. Department of Urology, China Medical University Hospital, Taichung, Taiwan

    Chao-Hsiang Chang

  4. Department of Urology, China Medical University Hsinchu Hospital, Hsinchu, Taiwan

    Sheng-Wei Li

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

    Chiu-Shong Liu

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

    Mu-Chi Chung

  7. Department of Chemistry, Fu Jen Catholic University, 510, Zhongzheng Road, Xinzhuang District, New Taipei City, 24205, Taiwan

    Wei-Ting Jung, Yen-Jung Kuo & Hui-Ling Lee

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  1. Chi-Jung Chung
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Contributions

Conceived and designed experiments: CJC, HTH, CHC, SWL, CSL, MCC, and HLL

Conducted experiments: GWW, WTJ, YJK, and HLL

Analyzed data: CJC and HLL

Contributed material: CJC, CHC, CSL, MCC, and HLL

Drafted manuscript: CJC, HTH, and HLL

Corresponding authors

Correspondence to Chi-Jung Chung or Hui-Ling Lee.

Ethics declarations

This study was approved by the Research Ethics Committee of China Medical University Hospital, Taichung, Taiwan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Responsible editor: Lotfi Aleya

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Chung, CJ., Hsu, HT., Chang, CH. et al. Relationships among cigarette smoking, urinary biomarkers, and urothelial carcinoma risk: a case-control study. Environ Sci Pollut Res 27, 43177–43185 (2020). https://doi.org/10.1007/s11356-020-10196-2

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