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.
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.
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转运蛋白有机阳离子转运蛋白 2 (OCT2)、多药和毒素挤出 1 (MATE1) 和 ATP 结合盒亚家族 C 成员 2 (ABCC2) 的遗传多态性与非 SM 患者铂类化疗反应和毒性的关联
DOI：
10.1186/s40880-016-0145-8
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发表时间：
2016-09-02
影响因子：
--
通讯作者：
Liu ZQ
中科院分区：
文献类型：
--
作者：
Qian CY;Zheng Y;Wang Y;Chen J;Liu JY;Zhou HH;Yin JY;Liu ZQ
背景：铂类化疗是非小细胞肺癌（NSCLC）的一线治疗，因此发现可用于预测该治疗疗效和毒性的生物标志物非常重要。四种重要的转运蛋白基因在肾脏中表达，包括有机阳离子转运蛋白2（OCT 2）、多药和毒素排出1（MATE 1）、ATP结合盒亚家族B成员1（ABCB 1）和ATP结合盒亚家族C成员2（ABCC 2），这些基因的遗传多态性可能改变铂类药物的疗效和不良反应。本研究旨在探讨这些转运蛋白基因多态性与非小细胞肺癌患者铂类药物化疗反应和毒性的关系。所有患者均为新诊断的NSCLC患者，并接受了至少两个周期的含铂化疗。治疗2个周期后评价肿瘤反应和毒性，并提取患者的基因组DNA。结果：OCT 2 rs316019与铂类药物的肝毒性（P = 0.026）和血液学毒性（P = 0.039）相关，MATE 1 rs 2289669与铂类药物的血液学毒性相关（P = 0.016）。此外，ABCC 2 rs717620与铂类化疗反应显著相关（P = 0.031）。结论：OCT 2 rs316019、MATE 1 rs 2289669和ABCC 2 rs717620基因多态性可能是预测非小细胞肺癌铂类药物化疗毒副反应的潜在临床指标。试验注册中国临床试验注册中心ChiCTR-RNC-12002892。
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 (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.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 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.Conclusion: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.
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影响因子：
--
作者：
Kathawala RJ;Wang YJ;Shukla S;Zhang YK;Alqahtani S;Kaddoumi A;Ambudkar SV;Ashby CR Jr;Chen ZS
通讯作者：
Chen ZS
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
3.7
作者：
Terada, Tomohiro;Masuda, Satohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi
影响因子：
5.8
作者：
Tanihara, Yuko;Masuda, Satohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi
影响因子：
3.7
作者：
Yin JY;Huang Q;Zhao YC;Zhou HH;Liu ZQ
通讯作者：
Liu ZQ