Associations ofgenetic polymorphisms ofthe transporters organic cation transporter 2 (OCT2), multidrug andtoxin extrusion 1 (MATE1), andATP-binding cassette subfamily C member 2 (ABCC2) withplatinum-based chemotherapy response andtoxicity innon-small cell lung cancer patients
10.1186/s40880-016-0145-8
- Author:
ChenYueQian
1
;
YiZheng
;
YingWang
;
JuanChen
;
JunYanLiu
;
HongHaoZhou
;
JiYeYin
;
Liu ZHAOQIAN
Author Information
1. Department of Clinical Pharmacology
- Keywords:
OCT2;
MATE1;
ABCC2;
Non-small cell lung cancer;
Platinum-based chemotherapy
- From:Chinese Journal of Cancer
2016;56(11):604-616
- CountryChina
- Language:Chinese
-
Abstract:
Background:Platinum?based chemotherapy is the ifrst?line treatment of non?small cell lung cancer (NSCLC); it is therefore important to discover biomarkers that can be used to predict the effcacy 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 effcacy 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. 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 chemo?therapy toxicity and response. Results: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 signiifcantly associated with the platinum?based chemotherapy response (P=0.031).ABCB1 polymor?phisms were associated with neither response nor toxicity. Conclusion:OCT2 rs316019,MATE1 rs2289669, andABCC2 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
