Carcinogen associated with A:T to T:A transversions in tumor suppressor and oncogenes
FRIDAY, April 13 (HealthDay News) -- A carcinogen produced by Aristolochia plants, which are commonly used in herbal remedies in Taiwan, is associated with signature types of DNA damage linked to aristolochic acid in Taiwanese patients with urothelial carcinoma of the upper urinary tract (UUC), according to a study published online April 9 in the Proceedings of the National Academy of Sciences.
Noting that aristolochic acid is known to be toxic and carcinogenic to the kidney, Chung-Hsin Chen, from the National Taiwan University Hospital in Taipei, and colleagues examined biomarkers associated with UUC in 151 UUC patients and 25 patients with renal cell carcinoma as controls; all patients lived in Taiwan. The authors note that the incidence of UUC in Taiwan is the highest in the world.
The researchers found that patients with UUC had a unique mutational signature in the TP53 tumor suppressor gene, including A:T to T:A transversion, that was identical to the signature found in Balkan endemic nephropathy, which is linked to ingestion of Aristolochia clematitis in wheat. These transversions were also found in the FGFR3 and HRAS oncogenes, in activating positions. Aristolactam-DNA adducts were found in the renal cortex of 83 percent of patients with A:T to T:A mutations in any of these genes.
"We conclude that exposure to aristolochic acid contributes significantly to the incidence of UUC in Taiwan, a finding with significant implications for global public health," Chen and colleagues write.
One author is an employee of Roche Molecular Systems, where the Amplichip p53 test used in this study is being developed.
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