Associations of genetic polymorphisms of the transporters organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATE1),and ATP-binding cassette subfamily C member 2(ABCC2) with platinum-based chemotherapy response and toxicity in non-small cel  

作　　者：Chen-Yue Qian Yi Zheng Ying Wang Juan Chen Jun-Yan Liu Hong-Hao Zhou Ji-Ye Yin Zhao-Qian Liu 

机构地区：[1]Department of Clinical Pharmacology,Xiangya Hospital,Central South Uni-versity,Changsha 410008,Hunan,P.R.China. [2]Institute of Clinical Pharmacol-ogy,Hunan Key Laboratory of Pharmacogenetics,Central South University,Changsha 410078,Hunan,P.R.China. [3]Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study,Hengyang 421001,Hunan,P.R.China. [4]Key Laboratory of Hunan Province for Traditional Chinese Medicine in Obstetrics&Gynecology Research,The Maternal and Child Health Hospital of Hunan Province,Changsha 410008,Hunan,P.R.China. [5]The affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,Changsha 410008,Hunan,P.R.China. [6]Xiangya School of Medicine,Central South University,Changsha 410008,Hunan,P.R.China.

出　　处：《Chinese Journal of Cancer》2016年第11期604-616,共13页

基　　金：supported by the National High-tech R&D Program of China(863 Program)(2012AA02A517);National Natural Science Foundation of China(81173129,81202595,81373490,81273595)

摘　　要：Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial RegistryBackground：Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer（NSCLC）;it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2（OCT2）,multidrug and toxin extrusion 1（MATEl）,ATP-binding cassette subfamily B member 1 {ABCB1）,and ATP-binding cassette subfamily C member 2（ABCC2）,and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods：A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients＇ genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results：OCT2 rs316019 was associated with hepatotoxicity（P = 0.026） and hematological toxicity（P = 0.039）,and MATEl rs2289669 was associated with hematological toxicity induced by platinum（P = 0.016）.In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response（P = 0.031）.ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion：OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry ChiCTR-RNC-12002892

关 键 词：OCT2 MATE1 ABCC2 Non-small cell lung cancer Platinum-based chemotherapy 

分 类 号：R734.2[医药卫生—肿瘤]