Risk Assessment of Upper Tract Urothelial Carcinoma Related to Aristolochic Acid

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 22; no. 5; pp. 812 - 820
• Main Authors: WU, Felicia, TIANXIU WANG
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.05.2013
• Subjects: Aristolochic Acids - administration & dosage; Aristolochic Acids - adverse effects; Biological and medical sciences; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - adverse effects; Humans; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - epidemiology; Kidney Failure, Chronic - genetics; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Risk Assessment; Risk Factors; Tumors; Tumors of the urinary system; Urethral Neoplasms - chemically induced; Urethral Neoplasms - epidemiology; Urethral Neoplasms - genetics; Urinary tract. Prostate gland; Urinary system disease; Cancerology; Acids; Risk factor; Risk; Urinary tract disease; Malignant tumor; Upper urinary tract transitional cell carcinoma; Cancer
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.epi-12-1386

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 objective was to estimate cumulative exposures of aristolochic acid associated with 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). Using epidemiologic studies on aristolochic acid-related disease from multiple different 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. Mean values for risk ratios, ORs, RRs, or HRs, of UUC caused by aristolochic acid ranged from 1 to 49. A meta-analysis of these studies resulted in a pooled OR of 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. Aristolochic acid exposure is significantly associated with an increased risk of UUC, and there is a dose-dependent relationship between cumulative aristolochic acid exposure and ESRD risk. 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 of Aristolochia plants with harvested food crops.