https://scholars.lib.ntu.edu.tw/handle/123456789/521202
標題: | Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia | 作者: | Ng A.W.T. Poon S.L. Huang M.N. Lim J.Q. Boot A. Yu W. Suzuki Y. Thangaraju S. Ng C.C.Y. Tan P. Pang S.-T. Huang H.-Y. Yu M.-C. PO-HUANG LEE Hsieh S.-Y. Chang A.Y. Teh B.T. Rozen S.G. |
公開日期: | 2017 | 出版社: | American Association for the Advancement of Science | 卷: | 9 | 期: | 412 | 起(迄)頁: | eaan6446 | 來源出版物: | Science Translational Medicine | 摘要: | 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 bemuchmore 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. ? Copyright 2017 The Authors. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85031791401&doi=10.1126%2fscitranslmed.aan6446&partnerID=40&md5=211b0371003b13ef07c6e0b047573fe4 https://scholars.lib.ntu.edu.tw/handle/123456789/521202 |
ISSN: | 1946-6234 | DOI: | 10.1126/scitranslmed.aan6446 | SDG/關鍵字: | aristolochic acid; aristolochic acid; adult; Article; Europe; exposure; female; geographic distribution; herbal medicine; human; Japan; Korea; liver cell carcinoma; major clinical study; male; mutational analysis; North America; priority journal; sex difference; Taiwan; tumor gene; whole exome sequencing; Asia; genetics; geography; immunotherapy; liver tumor; mutagenesis; mutation; Aristolochic Acids; Asia; Geography; Humans; Immunotherapy; Liver Neoplasms; Mutagenesis; Mutation; Taiwan |
顯示於: | 醫學系 |
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