Predictive assessment in pharmacogenetics of Glutathione S-transferases genes on efficacy of platinum-based chemotherapy in non-small cell lung cancer patients.
Predictive assessment in pharmacogenetics of Glutathione S-transferases genes on efficacy of platinum-based chemotherapy in non-small cell lung cancer patients.
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谷胱甘肽S-转移酶基因药物遗传学对非小细胞肺癌患者铂类化疗疗效的预测评估
DOI：
10.1038/s41598-017-02833-7
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发表时间：
2017-06-01
影响因子：
4.6
通讯作者：
Qu J
中科院分区：
文献类型：
--
作者：
Ye H;Shao M;Shi X;Wu L;Xu B;Qu Q;Qu J
在以往的研究中，谷胱甘肽S转移酶P1、M1和T1变异对非小细胞肺癌患者以铂为主的化疗疗效的影响是不一致的。我们的荟萃分析纳入了31篇文献，包括5712名患者，并提供了更令人信服和可靠的结论。结果显示，GSTP1IIe105Val IIe/Val和Val/Val亚裔患者的有效率高于IIe/IIe患者(优势比(OR) = 为1.592，95%可信区间(CI)为1.087~2.332，P= 0.017)。携带有利的GSTM1缺失基因的亚洲患者比携带不利的GSTM1缺失基因的患者更有可能对以铂为基础的化疗有更好的缓解率(OR = 1.493(1.192-1.870)，P<； 0.001)。携带GSTT1缺失型的高加索肺癌患者较GSTT1缺失型患者的生存时间短、死亡风险高(危险比(HR) = 1.423，CI = 1.084~1.869，P= 0.011)。我们的荟萃分析提示，GSTP1IIe105Val、GSTM1和GSTT1零变异可能是非小细胞肺癌患者铂类化疗疗效的预测因素。使用GSTP1IIe105Val、GSTM1和GSTT1零基因多态作为以铂为基础的个体化化疗对非小细胞肺癌患者疗效的预测因素，需要多中心、多种族和大样本药物遗传学研究的进一步验证。
The influences of glutathione s-transferase P1, M1, and T1 variants on the efficacy of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients were inconsistent in previous studies. Our meta-analysis enrolled 31 publications including 5712 patients and provided more convincing and reliable conclusions. Results showed thatGSTP1IIe105Val IIe/Val and Val/Val Asian patients were more likely to have better response rates compared to IIe/IIe patients (odds ratio (OR) = 1.592, 95% confidence intervals (CIs), 1.087–2.332,P= 0.017). The Asian patients bearing the favorableGSTM1null genotype were more likely to have better response rates to platinum-based chemotherapy compared to those patients with the unfavorableGSTM1present genotype (OR = 1.493 (1.192–1.870),P< 0.001). Caucasian lung cancer patients bearingGSTT1null genotype might be more closely associated with shorter survival time and higher risks of death than theGSTT1present patients (hazard ratio (HR) = 1.423, CI = 1.084–1.869,P= 0.011). Our meta-analysis suggested that theGSTP1IIe105Val,GSTM1andGSTT1null variants might be predictive factors for the efficacy of platinum-based chemotherapy to NSCLC patients. The use ofGSTP1IIe105Val,GSTM1andGSTT1null polymorphisms as predictive factors of efficacy of personalized platinum-based chemotherapy to NSCLC patients requires further verification with multi-center, multi-ethnic and large-sample-size pharmacogenetic studies.