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

• Published in: World journal of urology Vol. 41; no. 4; pp. 899 - 907
• Main Authors: Dickman, Kathleen G., Chen, Chung-Hsin, Grollman, Arthur P., Pu, Yeong-Shiau
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2023; Springer Nature B.V
• Subjects: Aristolochia; Aristolochic acid; Aristolochic Acids - adverse effects; Aristolochic Acids - analysis; Biomarkers; Bladder cancer; Carcinogens; Carcinoma, Transitional Cell - chemically induced; Carcinoma, Transitional Cell - epidemiology; Carcinoma, Transitional Cell - genetics; Conserved sequence; Deoxyadenosine; DNA adducts; DNA Adducts - adverse effects; Drugs, Chinese Herbal - adverse effects; Epidemiology; Female; Herbal medicine; Humans; Kidney Neoplasms - chemically induced; Kidney Neoplasms - epidemiology; Kidney Neoplasms - genetics; Medicine; Medicine & Public Health; Mutation; Nephrectomy; Nephrology; Nephropathy; Nucleotide sequence; Oncology; Renal failure; Renal function; Taiwan - epidemiology; Topic Paper; Trinucleotide repeats; Ureteral Neoplasms - chemically induced; Ureteral Neoplasms - epidemiology; Urinary Bladder Neoplasms; Urinary Tract; Urogenital system; Urology; Urothelial carcinoma; Taiwan; Ureteral cancer; DNA adduct; Renal pelvic cancer; Nephropathy; Mass spectrometry; Aristolochia
• ISSN: 1433-8726; 0724-4983; 1433-8726
• DOI: 10.1007/s00345-022-04100-5

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.