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Aristolochic acid-containing Chinese herbal medicine and upper urinary tract urothelial carcinoma in Taiwan: a narrative review

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Abstract

Purpose

The high incidence of upper urinary tract urothelial carcinoma (UTUC) in Taiwan is largely due to exposure to aristolochic acid (AA), a principal component of Aristolochia-based herbal medicines. Here we systematically review the molecular epidemiology, clinical presentation and biomarkers associated with AA-induced UTUC.

Methods

This is a narrative review. Medline, Embase, and Web of Science were searched from inception to December 31, 2021. Studies evaluating the association, detection, and clinical characteristics of AA and UTUC were included.

Results

A nationwide database revealed 39% of the Taiwanese population had been exposed to AA-containing herbs between 1997 and 2003. Epidemiological reports revealed AA posed a significantly higher hazard for renal failure and UTUC in herbalists and the general population who ingested AA-containing herbs. The presence of aristolactam-DNA adducts and a distinctive signature mutation, A:T to T:A transversions, located predominantly on the non-transcribed DNA strand, with a strong preference for deoxyadenosine in a consensus sequence (CAG), was observed in many UTUC patients. Clinically, AA-related UTUC patients were characterized by a younger age, female gender, impaired renal function and recurrence of contralateral UTUC. To date, there are no preventive measures, except prophylactic nephrectomy, for subjects at risk of AA nephropathy or AA-related UTUC.

Conclusion

AA exposure via Aristolochia-based herbal medicines is a problem throughout Taiwan, resulting in a high incidence of UTUC. Aristolactam-DNA adducts and a distinctive signature mutation, A:T to T:A transversions, can be used as biomarkers to identify AA-related UTUC. AA-related UTUC is associated with a high recurrence rate of contralateral UTUC.

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Authors and Affiliations

  1. Departments of Pharmacological Sciences and Medicine, Stony Brook University, Stony Brook, NY, USA

    Kathleen G. Dickman & Arthur P. Grollman

  2. Department of Urology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan, ROC

    Chung-Hsin Chen & Yeong-Shiau Pu

Authors
  1. Kathleen G. Dickman
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  2. Chung-Hsin Chen
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  3. Arthur P. Grollman
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  4. Yeong-Shiau Pu
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Contributions

KGD: project development, data analysis, manuscript writing. CHC: project development, data collection, data analysis, manuscript writing. APG: project development, manuscript editing. YSP: project development, manuscript editing.

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Correspondence to Chung-Hsin Chen.

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Research involving human participants and animals

Not applicable. In this article, we systemically reviewed the published studies associated with aristolochic acid and did not reveal new information obtained from human or animal studies.

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Dickman, K.G., Chen, CH., Grollman, A.P. et al. Aristolochic acid-containing Chinese herbal medicine and upper urinary tract urothelial carcinoma in Taiwan: a narrative review. World J Urol 41, 899–907 (2023). https://doi.org/10.1007/s00345-022-04100-5

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