title: 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 cell lung cancer patients.
abstract: 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 (MATE1), 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 platinum-based chemotherapy response and toxicity in NSCLC patients.
  
  
  
  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.
  
  
  
  OCT2 rs316019 was associated with hepatotoxicity (P = 0.026) and hematological toxicity (P = 0.039), and MATE1 rs2289669 was associated with hematological toxicity induced by platinum (P = 0.016). In addition, ABCC2 rs717620 was significantly associated with the platinum-based chemotherapy response (P = 0.031). ABCB1 polymorphisms were associated with neither response nor toxicity.
  
  
  
  OCT2 rs316019, MATE1 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.
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors: Chen-Yue
authors: CY
authors: Qian
authors: 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.
authors: Yi
authors: Y
authors: Zheng
authors: The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, P. R. China.
authors: Ying
authors: Y
authors: Wang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors: Juan
authors: J
authors: Chen
authors: Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, P. R. China.
authors: Jun-Yan
authors: JY
authors: Liu
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors: Hong-Hao
authors: HH
authors: Zhou
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors: Ji-Ye
authors: JY
authors: Yin
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China. liuzhaoqian63@126.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China. liuzhaoqian63@126.com.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China. liuzhaoqian63@126.com.
authors: Zhao-Qian
authors: ZQ
authors: Liu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D000075102:Organic Cation Transporter 2; D000068437:Pemetrexed / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D016190:Carboplatin; D002945:Cisplatin; D003841:Deoxycytidine; D000077143:Docetaxel; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D000068437:Pemetrexed; D043823:Taxoids; D000093542:Gemcitabine; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C491013:SLC22A2 protein, human; C521869:SLC47A1 protein, human
keywords: ABCC2; MATE1; Non-small cell lung cancer; OCT2; Platinum-based chemotherapy