封面论文!Science子刊:草药的阴暗面——引发肝癌
2017/10/20
10月18日,最新一期Science Translational Medicine的封面文章讲述了“草药的黑暗面”:来自新加坡的一个科学家小组揭示了在亚洲地区肝癌与传统中草药之间存在关联的广泛证据。研究称,需要采取更有力的措施来防止人们食用一种被称为马兜铃酸的化学物质。


图片来源:Science Translational Medicine

马兜铃酸(aristolochic acids,AA)是一种草药化合物,先前曾被发现与肾衰竭和泌尿道癌症有关。由于存在这些已知的毒性,含有这种化合物的药草在一些国家被限制或禁止,但实际上,人们依然可以从互联网和一些替代配方中接触到马兜铃酸。

通过对大量的样本进行分析,这项新研究指出,马兜铃酸在亚洲地区的使用依然很普遍,并且它似乎增加了患多种不同癌症类型的风险。


图片来源:Science Translational Medicine

研究者们表示,尽管先前已发现,AA与多种癌症相关,有时会引发非常高的突变负荷,但AA在肝细胞癌(hepatocellular carcinomas,HCCs)中的作用仍是未知的。在这项研究中,他们首先对来自中国台湾两家医院的98个HCCs样本进行了全外显子组测序,结果发现,有78%的样本显示出与AA相关的独特突变特征。


图片来源:Science Translational Medicine

然后,他们在来自不同地理区域的1400个HCCs样本中搜索AA相关的突变特征。结果发现,来自中国内地患者的89个HCCs样本中有47%具有AA相关的突变特征。此外,越南的26个样本中有5个显示与AA有关,比例为19%;其它东南亚国家的9个肿瘤样本中,有5个与马兜铃酸有关,比例为56%。

与亚洲相比,在北美,肝癌与AA的关联并不常见:被研究的209个样本中,只有4.8%与马兜铃酸有关;此外,来自欧洲的230个样本中,只有1.7%的比例存在上述关联。

研究称,由于没有直接的禁令,以及只有特定的植物(而不是任何含有马兜铃酸及其衍生物的植物和产品)被监管,这使得消费者很难完全避开这类化合物。作者们在结论中强调,建议采取进一步的措施,避免人们接触和使用马兜铃酸。

参考资料:

Across Asia, liver cancer is linked to herbal remedies: study

Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia

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  • Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia

    Many traditional pharmacopeias include Aristolochia and related plants, which contain nephrotoxins and mutagens in the form of aristolochic acids and similar compounds (collectively, AA). AA is implicated in multiple cancer types, sometimes with very high mutational burdens, especially in upper tract urothelial cancers (UTUCs). AA-associated kidney failure and UTUCs are prevalent in Taiwan, but AA’s role in hepatocellular carcinomas (HCCs) there remains unexplored. Therefore, we sequenced the whole exomes of 98 HCCs from two hospitals in Taiwan and found that 78% showed the distinctive mutational signature of AA exposure, accounting for most of the nonsilent mutations in known cancer driver genes. We then searched for the AA signature in 1400 HCCs from diverse geographic regions. Consistent with exposure through known herbal medicines, 47% of Chinese HCCs showed the signature, albeit with lower mutation loads than in Taiwan. In addition, 29% of HCCs from Southeast Asia showed the signature. The AA signature was also detected in 13 and 2.7% of HCCs from Korea and Japan as well as in 4.8 and 1.7% of HCCs from North America and Europe, respectively, excluding one U.S. hospital where 22% of 87 “Asian” HCCs had the signature. Thus, AA exposure is geographically widespread. Asia, especially Taiwan, appears to be much more extensively affected, which is consistent with other evidence of patterns of AA exposure. We propose that additional measures aimed at primary prevention through avoidance of AA exposure and investigation of possible approaches to secondary prevention are warranted.

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