Epigenomics and Mechanisms Branch, International Agency for Research on Cancer WHO, Lyon, France.
BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czech Republic.
Nat Rev Cancer. 2022 Oct;22(10):576-591. doi: 10.1038/s41568-022-00494-x. Epub 2022 Jul 19.
Aristolochic acids (AAs) are a group of naturally occurring compounds present in many plant species of the Aristolochiaceae family. Exposure to AA is a significant risk factor for severe nephropathy, and urological and hepatobiliary cancers (among others) that are often recurrent and characterized by the prominent mutational fingerprint of AA. However, herbal medicinal products that contain AA continue to be manufactured and marketed worldwide with inadequate regulation, and possible environmental exposure routes receive little attention. As the trade of food and dietary supplements becomes increasingly globalized, we propose that further inaction on curtailing AA exposure will have far-reaching negative effects on the disease trends of AA-associated cancers. Our Review aims to systematically present the historical and current evidence for the mutagenicity and carcinogenicity of AA, and the effect of removing sources of AA exposure on cancer incidence trends. We discuss the persisting challenges of assessing the scale of AA-related carcinogenicity, and the obstacles that must be overcome in curbing AA exposure and preventing associated cancers. Overall, this Review aims to strengthen the case for the implementation of prevention measures against AA's multifaceted, detrimental and potentially fully preventable effects on human cancer development.
马兜铃酸（AAs）是存在于马兜铃科多种植物中的一组天然化合物。接触 AAs 是导致严重肾病以及泌尿系统和肝胆系统癌症（以及其他癌症）的一个重要危险因素，这些癌症通常具有复发性，并以 AAs 显著的突变特征为特征。然而，含有 AAs 的草药药物仍在全球范围内制造和销售，监管不足，对可能的环境暴露途径关注甚少。随着食品和膳食补充剂贸易的全球化程度不断提高，如果不对 AAs 的暴露加以控制，将会对 AAs 相关癌症的疾病趋势产生深远的负面影响。我们的综述旨在系统地介绍 AAs 的致突变性和致癌性的历史和当前证据，以及消除 AAs 暴露源对癌症发病率趋势的影响。我们讨论了评估 AAs 相关性致癌性规模所面临的持续挑战，以及在遏制 AAs 暴露和预防相关癌症方面必须克服的障碍。总的来说，本综述旨在加强实施预防措施的理由，以应对 AAs 对人类癌症发展的多方面、有害且潜在完全可预防的影响。
