PURPOSE OF REVIEW: To acquaint urologists with aristolochic acid nephropathy, an iatrogenic disease that poses a distinct threat to global public health. In China alone, 100 million people may currently be at risk. We illustrate the power of molecular epidemiology in establishing the cause of this disease. RECENT FINDINGS: Molecular epidemiologic approaches and novel mechanistic information established a causative linkage between exposure to aristolochic acid and urothelial carcinomas of the bladder and upper urinary tract. Noninvasive tests are available that detect urothelial cancers through the genetic analysis of urinary DNA. Combined with cytology, some of these tests can detect 95% of patients at risk of developing bladder and/or upper urothelial tract cancer. Robust biomarkers, including DNA-adduct and mutational signature analysis, unequivocally identify aristolochic acid-induced tumours. The high mutational load associated with aristolochic acid-induced tumours renders them candidates for immune-checkpoint therapy. SUMMARY: Guided by recent developments that facilitate early detection of urothelial cancers, the morbidity and mortality associated with aristolochic acid-induced bladder and upper tract urothelial carcinomas may be substantially reduced. The molecular epidemiology tools that define aristolochic acid-induced tumours may be applicable to other studies assessing potential environmental carcinogens.

Department of Medicine Stony Brook University Stony Brook New York USA

Department of Pharmacological Sciences

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Austria

Department of Urology University of Texas Southwestern Dallas Texas USA

Department of Urology Weill Cornell Medical College New York New York

Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

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Aristolochic acid-associated cancers: a public health risk in need of global action