Katharina Rebhan1, Iris E Ertl1, Shahrokh F Shariat1,2,3,4,5,6, Arthur P Grollman7,8, Thomas Rosenquist7. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Austria. 2. Department of Urology, Weill Cornell Medical College, New York, New York. 3. Department of Urology, University of Texas Southwestern, Dallas, Texas, USA. 4. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. 5. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. 6. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan. 7. Department of Pharmacological Sciences. 8. Department of Medicine, Stony Brook University, Stony Brook, New York, USA.
Abstract
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.
PURPOSE OF REVIEW: To acquaint urologists with aristolochic acidnephropathy, 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.
Authors: Sandra Karanović; Maude Ardin; Zuojian Tang; Karla Tomić; Stephanie Villar; Claire Renard; Elisa Venturini; Adam H Lorch; Daniel S Lee; Želimir Stipančić; Neda Slade; Ivana Vuković Brinar; Damir Dittrich; Krešimir Karlović; Fran Borovečki; Kathleen G Dickman; Magali Olivier; Arthur P Grollman; Bojan Jelaković; Jiri Zavadil Journal: Int J Cancer Date: 2021-10-15 Impact factor: 7.316