Traditional Chinese herbal remedy implicated in cancers cases
Washington: Scientists have used genome sequencing to prove that traditional Chinese herbal remedy, aristolochic acid, causes upper urinary tract cancers.
The aristolochic acid is a plant compound contained in herbal remedies used for thousands of years to treat a variety of ailments like arthritis, gout and inflammation.
Aristolochic [pronounced a-ris-to-lo-kik] acid is found in the plant family "Aristolochia," a vine known widely as birthwort, and while the U.S. Food and Drug Administration first warned of its cancer-causing potential in 2001, botanical products and herbal remedies containing it can still be purchased online.
Moreover, the vine has been found to be an environmental carcinogen through the contamination of food supplies of farming villages in the Balkans, where Aristolochia grows wildly in the local wheat fields.
For years, scientists have known of some mutations in upper urinary tract cancer patients exposed to the plant toxin. But the genome-wide spectrum of mutations associated with aristolochic acid exposure remained largely unknown.
For the current study, the Johns Hopkins and Stony Brook team used whole-exome sequencing on 19 Taiwanese upper urinary tract cancer patients exposed to aristolochic acid, and seven patients with no suspected exposure to the toxin.
The technique scours the exome, part of the human genome that contains codes for functional proteins and can reveal particular mutations, in this case, those associated with cancer.
Kenneth Kinzler, Ph.D., professor of oncology in the Johns Hopkins Kimmel Cancer Center`s Ludwig Center for Cancer Genetics and Therapeutics, said that genome-wide sequencing has allowed us to tie aristolochic acid exposure directly to an individual getting cancer.
He said that the technology gives us the recognizable mutational signature to say with certainty that a specific toxin is responsible for causing a specific cancer.
Kinzler added that their hope is that using the more targeted whole-exome-sequencing process will provide the necessary data to guide public health decisions related to cancer prevention.
Specifically, Kinzler says they found an average of 753 mutations in each tumor from the toxin-exposed group compared with 91 in tumors from the non-exposed group.
The toxin-exposed group had a large number of a particular, rare type of mistake (a mutational signature) in the ATCG chemical code of their DNA.
The predominant mutation type in the toxin-exposed tumors (72 percent) was an A substituted with a T. In one instance, the scientists used the mutational signature to uncover an artistolochic-related tumor in a patient who was unaware of prior exposure.
The findings have been published in Science Translational Medicine.