A component of a plant used in Chinese herbal remedies, has been found to be associated with upper urothelial cancer (UUC), reports a study in Kidney International. In the study Arthur Grollman and colleagues ,from Stony Brook University School of Medicine (New York, USA) , were investigating whether Balkan endemic nephropathy, a disease limited to rural areas in the Danube river basin, characterised by progressive kidney failure and the development of UUC was linked to exposure to the plant Aristolochia clematis (also known as birthwort). In these areas Aristolochia is known to grow intermixed with wheat, leading to suggestions that toxin exposure occurs through ingestion of bread made from contaminated grain. In the study Grollman and colleagues extracted DNA from the tumours of 67 patients with UUC living in a region known to harbour endemic neuropathy.
In these samples they detected that a metabolite of aristolochic acid was bound to DNA in the kidney cortex of the patients. In addition, the team identified that the patients had unique mutations in TP53, a tumour suppressor gene involved in many cancers. In contrast, neither the aristolactam-DNA adducts or the specific mutations could be detected in the tissues of patients with UUC residing in non endemic regions.
"This molecular epidemiologic study provides evidence not only that genetically susceptible individuals exposed to the toxin likely will develop the disease, but also provides a solid foundation for public health officials to develop strategies designed to eliminate endemic neuropathy," said Grollman. With aristolochic acid known to be found in herbal remedies and homeopathic treatment, say the researchers, the studies have implications that go far beyond the Balkan region. The presence of DNA adducts in the kidney along with the specific mutation in TP53, suggest the researchers, could be used as a biomarker to identify individuals at risk of developing UUC.