Chen Xuewei, Liu Liping, Guo Zhihua, Liang Wenhua, He Jiaxi, Huang Liyan, Deng Qiuhua, Tang Hailing, Pan Hui, Guo Minzhang, Liu Yang, He Qihua, He Jianxing
Department of Thoracic Surgery, Guangzhou Institute of Respiratory Disease and State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, No 151, Yanjiang Rd, Guangzhou, 510120, Guangdong, People's Republic of China.
The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
Cancer Chemother Pharmacol. 2017 Jun;79(6):1109-1117. doi: 10.1007/s00280-017-3306-9. Epub 2017 May 13.
Previous studies of irinotecan pharmacogenetics have shown that the UGT1A128 polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians. Yet compared with the UGT1A16 mutation, the UGT1A128 occurs at a much lower frequency in the Asians. Whether UGT1A16 and UGT1A128 are associated with IRI-induced neutropenia, diarrhea and IRI-based chemotherapy tumor response (TR) in Asians with lung cancer remains controversial. In this meta-analysis, we found a higher risk of neutropenia and diarrhea with IRI-based chemotherapy in Asians with lung cancer carrying the UGT1A16 polymorphism. However, UGT1A128 showed a weak correlation with diarrhea, but no significant correlation with neutropenia. Neither UGT1A16 nor UGT1A128 is associated with IRI-based chemotherapy TR. These data suggest that the UGT1A128 polymorphism may not be a suitable biomarker to predict IRI-induced toxicities and chemotherapy TR in Asians, while UGT1A*6 polymorphism is associated with a higher risk of IRI-induced neutropenia and diarrhea, but not IRI-based chemotherapy TR.
先前关于伊立替康药物遗传学的研究表明，UGT1A128多态性对高加索人中伊立替康（IRI）诱导的毒性有影响。然而，与UGT1A16突变相比，UGT1A128在亚洲人中的发生频率要低得多。UGT1A16和UGT1A128是否与肺癌亚洲患者中IRI诱导的中性粒细胞减少、腹泻以及基于IRI的化疗肿瘤反应（TR）相关仍存在争议。在这项荟萃分析中，我们发现携带UGT1A16多态性的肺癌亚洲患者接受基于IRI的化疗时，发生中性粒细胞减少和腹泻的风险更高。然而，UGT1A128与腹泻的相关性较弱，与中性粒细胞减少无显著相关性。UGT1A16和UGT1A128均与基于IRI的化疗TR无关。这些数据表明，UGT1A128多态性可能不是预测亚洲人IRI诱导的毒性和化疗TR的合适生物标志物，而UGT1A*6多态性与IRI诱导的中性粒细胞减少和腹泻的较高风险相关，但与基于IRI的化疗TR无关。
