Herbs with AAs linked to HCC among Asians: What’s the evidence?
Herbal medicines containing nephrotoxins and mutagens in the form of aristolochic acids (AAs) have been previously linked to kidney failure and urinary tract cancer and are banned in some countries in Asia. Still, people are picking them up off the shelf in alternate formulations, unmindful of an equally deadly threat – liver cancer.
In a mutational analysis of 98 hepatocellular carcinomas (HCCs) from Taiwan, the distinct mutational signature of AA exposure was found in 78 percent of cases, accounting for 299 of 505 nonsilent mutations in known cancer driver genes. AA signature in 1,400 HCC samples from diverse regions in Asia also showed that 47 percent of HCCs in Chinese patients had the same mutational signature, although with lower mutational loads compared to what was observed in Taiwan. [Sci Transl Med 2017; doi:10.1126/scitranslmed.aan6446]
“This suggests that AA is involved in a remarkable proportion of liver cancers in Asia,” said primary investigator Professor Steven Rozen of the Cancer and Stem Cell Biology Programme and director at the Center for Computational Biology at the Duke-NUS Medical School in Singapore.
“Of note, AA signature mutations were found in 29 percent of HCCs from Southeast Asia, 13 percent from Korea, and 2.7 percent from Japan. The AA mutations were only found in 4.8 percent and 1.7 percent of HCCs from North America and Europe, respectively,” said Rozen.
“Plants known to contain high concentrations of AAs are easily available on the internet,” he added. In the US, herbs containing AAs are not regulated, provided they are labeled correctly. The US Food and Drug Administration has however issued warnings against its use.
In 2003, Taiwan banned AA-containing herbal remedies. China followed suit, restricting the use of certain AA-containing herbs. In the current study, AA signature mutation burdens were lower in China (median, 0.29 AA signature mutations/Mb) than in Taiwan (median, 2.26 AA signature mutations/Mb). There was also no significant difference in the prevalence of AA signature in HCCs diagnosed before and after the AA ban in Taiwan. One possible explanation to this, Rozen said, could be the continued use of AA-containing herbal medicines.
AA likely induces specific cancer-causing changes in liver DNA, potentially leading to HCC. Currently, there is no treatment specific to AA-associated HCCs and patients with this type of cancer are presumably also at increased risk for urinary tract cancers, in addition to kidney failure, warned Rozen. “Consumers should avoid herbs that contain AAs … though this is easier said than done.”
The findings present substantial opportunities for both primary and secondary prevention of HCC, the researchers said. Clinicians in Asia may want to counsel their patients on the risks of using herbal remedies containing AAs and their derivatives as it is a more common practice in Asia than anywhere in the world.