Aristolochic acid (AA) is widely recognised to cause kidney failure, as well as kidney and urinary tract cancers. The mutagen has now been implicated in liver cancer, revealed the research team, led by the Duke NUS Medical School, Singapore.
Using DNA mutational signature analysis, the scientists examined data on 1400 liver cancers from different countries. They found the AA signature present in 78% of the liver cancer cases in Taiwan, 47% in China and 29% in Southeast Asia.
"Although we knew that there was exposure to AA in Taiwan, we were very surprised to find such a high proportion of liver cancer sufferers had exposure to AA," said co-author Professor Sen-Yung Hsieh from the Chang Gung Memorial Hospital, Taiwan.
"We did not suspect that exposure to AA was so prevalent in so many different areas," commented study leader Professor Steven Rozen. “This also was an unexpected finding.”
AA is a naturally occurring chemical in plants such as Asarum and Aristolochia. Historically, these plants have been used to treat many different ailments in Traditional Chinese Medicine (TCM) and as herbal remedies in other pharmacopeias for many years.
Lack of regulation
Regulation in Taiwan and China does not appear to be comprehensive. A ban on some, but not all, remedies containing AA was introduced in 2003 in Taiwan, while in China some restrictions are in place regarding their use in TCM.
“Medicinal use of AA-containing plants is only lightly regulated in many jurisdictions. The plants are not banned outright in China and even in Taiwan, to the best of our understanding, only specific plants, rather than any plant and product containing AA or its derivatives, are regulated,” the researchers noted.
“Strikingly, xi xin, the most commonly prescribed herb before 2003, is not banned,” they added.
Even in the US, AA-containing herbs can by-pass regulation, provided no health claims are made and that the remedies are correctly labelled. Additionally, plants containing AA or its derivatives are widely available on the internet.
Cancers continue despite ‘ban’
The researchers found no difference between the prevalence of AA signature in liver cancers diagnosed before and after the 2003 ‘ban’.
The scientists suggested that the number of AA-induced liver cancers may just be lagging the reduced exposure to AA (analogous to the rates of smoking-related lung cancer cases in the US only declining some decades after reduction in cigarette use).
However, the researchers also highlighted the possibility that TCM practitioners continued to prescribe AA-containing remedies after the ban – some evidence of which was confirmed. Continuing prescription may have been due to incorrect labelling, incomplete analysis of formulations or the failure of the ban to exclude all AA-containing plants.
Prevention measures needed
Due to the ongoing exposure to AA and the associated health consequences, urgent prevention measures are needed, suggest the researchers.
“In light of the wide availability of AA-containing plants, education and public awareness are paramount for primary prevention,” the team advocated.
“More thorough methods for testing herbal products, such as chromatographic fingerprinting, combined with regulatory oversight of the supply chain could also help reduce exposure.”
“Secondary prevention might take the form of enhanced screening for AA-associated cancers or for kidney disease in patients suspected or known to be exposed to AA,” they concluded.
Source: Science Translational Medicine
Volume 9, Issue 412, eaan6446 DOI: 10.1126/scitranslmed.aan6446
“Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia”
Authors: Alvin W. T. Ng, Steven T. Rozen et al.