Research Article Risk Assessment of Upper Tract Urothelial Carcinoma Related to Aristolochic Acid

Background: Aristolochic acid is a toxin found in plants of the genus Aristolochia, to which humans can be exposed either through certain Chinese herbal medicines or through inadvertent commingling with food crops. Our objectivewas to estimate cumulative exposures of aristolochic acid associatedwith increased risk of end-stage renal disease (ESRD), and to conduct a systematic review and meta-analysis on aristolochic acid-induced upper tract urothelial carcinoma (UUC). Methods:Using epidemiologic studies onaristolochic acid-relateddisease frommultipledifferent regions of the world, a systematic review was conducted in which relative risks (RR), HRs, and ORs were derived or extracted directly, and a meta-analysis was conducted. One study was used to estimate a benchmark dose lower confidence limit (BMDL) for aristolochic acid-related ESRD. Results:Mean values for risk ratios, ORs, RRs, or HRs, of UUC caused by aristolochic acid ranged from 1 to 49.Ameta-analysis of these studies resulted in apooledORof 5.97 [95%confidence interval (CI), 2.78–12.84] for this aristolochic acid-related cancer. The obtained BMDL for aristolochic acid-related ESRD was 0.42 g cumulative aristolochic acid exposure. Conclusions:Aristolochic acid exposure is significantly associatedwith an increased risk of UUC, and there is a dose-dependent relationship between cumulative aristolochic acid exposure and ESRD risk. Impact: Individuals who use certain Chinese herbal medicines may significantly increase their risk of developing UUC and/or ESRD, as would individuals who are inadvertently exposed to aristolochic acid through commingling ofAristolochia plants with harvested food crops. Cancer Epidemiol Biomarkers Prev; 22(5); 812–20. 2013 AACR