Geneticists confirm herbal remedy carcinogen

Geneticists confirm herbal remedy carcinogen

In a study that identifies the striking genetic changes caused by a herb compound, scientists have found a direct link between aristolochic acid - used in a traditional herbal remedy - and upper urinary tract cancers.

The researchers say their findings also show the power of genome-wide sequencing, the method they used to find the compound's mutation signature, to spot individual exposure to carcinogens.

They write about their work in an August 7th online issue of Science Translational Medicine.

Known carcinogen, found in birthwort plants

Aristolochic acid is found in a group of vine plants known as "Aristolochia," more commonly known as birthwort. The plant has been used for centuries in traditional Chinese medicine, and also by the Greeks and Egyptians before that, to ease childbirth, treat arthritis, and other conditions.

The US Food and Drug Administration (FDA) called for dietary supplements and other products containing aristolochic acid to be discontinued in 2001, when they first warned of the substance's cancer-causing potential.

Many countries have since banned it, and the International Agency for Research on Cancer (IARC) has classified herbal compounds derived from birthwort as Group 1 carcinogens, meaning there is evidence they cause cancer in humans.

However, botanical products and herbal remedies containing the compound can still be bought online.

Aristolochic acid also enters the food supply in some regions

Aristolochia is also an environmental carcinogen. For instance, in certain regions around the Danube in Croatia, Bosnia and Serbia, the vine grows wild in wheat fields around the farming villages, causing aristolochic acid to enter the local food supply.

A study published in 2011 found that dietary exposure to aristolochic acid causes endemic nephropathy and cancers of the upper urinary tract in genetically susceptible individuals in those regions.

Full picture of the genetic mutations linked to aristolochic acid

Although scientists have known for some time that aristolochic acid causes certain mutations in patients who develop urinary tract cancer after being exposed to it, until this study there was no genome-wide picture of the complete range of mutations.

For the study, researchers from the US and Taiwan used a particular genome-wide method called whole-exome sequencing on tumor tissue taken from 19 patients with upper urinary tract cancer who had been exposed to aristolochic acid, and seven patients with no suspected exposure to the compound.

Whole-exome sequencing looks only at the exome, the part of the human genome that contains instructions for making proteins, and can reveal certain mutations, such as those linked to cancer.

Genetic signature of the tumors

The team found an average of 753 mutations in each tumor from the exposed patients, compared to 91 in tumors from patients who had not been exposed to aristolochic acid.

This is a high level of mutation. For instance, it exceeds that found in melanoma caused by exposure to ultraviolet radiation and in lung cancer caused by smoking.

The exposed patients also showed a high level of a particularly rare type of mutation. 72% of their mutations were where an A was substituted with a T in the the ATCG chemical code of their DNA.

Using this mutational signature, the researchers were also able to identify an artistolochic-associated tumor in a patient who was unaware of having been exposed to the compound.

Method's potential for finding other carcinogens

The team suggests their approach could also be used to identify likely carcinogens in cancer clusters, where unusually large numbers of similar cancers occur either in a particular location, population, or period of time.

Co-author Kenneth Kinzler, a professor of oncology at Johns Hopkins in the US told the press:

The technology gives us the recognizable mutational signature to say with certainty that a specific toxin is responsible for causing a specific cancer.

Our 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."

Funds from the Virginia and DK Ludwig Fund for Cancer Research, the Commonwealth Foundation and the Howard Hughes Medical Institute helped finance the study.

Mutagens and carcinogens | Biomolecules | MCAT | Khan Academy (Video Medical And Professional 2020).

Section Issues On Medicine: Disease