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Predictive assessment in pharmacogenetics of Glutathione S-transferases genes on efficacy of platinum-based chemotherapy in non-small cell lung cancer patients

机译:谷胱甘肽S-转移酶基因对非小细胞肺癌患者铂类化疗疗效的药物遗传学预测评估

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摘要

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 that GSTP1 IIe105Val 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 favorable GSTM1 null genotype were more likely to have better response rates to platinum-based chemotherapy compared to those patients with the unfavorable GSTM1 present genotype (OR = 1.493 (1.192–1.870), P < 0.001). Caucasian lung cancer patients bearing GSTT1 null genotype might be more closely associated with shorter survival time and higher risks of death than the GSTT1 present patients (hazard ratio (HR) = 1.423, CI = 1.084–1.869, P = 0.011). Our meta-analysis suggested that the GSTP1 IIe105Val, GSTM1 and GSTT1 null variants might be predictive factors for the efficacy of platinum-based chemotherapy to NSCLC patients. The use of GSTP1 IIe105Val, GSTM1 and GSTT1 null 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.
机译:谷胱甘肽S-转移酶P1,M1和T1变异对非小细胞肺癌(NSCLC)患者铂类化学疗法疗效的影响在以前的研究中并不一致。我们的荟萃分析招募了31篇出版物,包括5712例患者,并提供了更令人信服和可靠的结论。结果显示,与IIe / IIe患者相比,GSTP1 IIe105Val IIe / Val和Val / Val亚洲患者更有可能具有更好的缓解率(几率(OR)= 1.592,95%置信区间(CIs),1.087–2.332,P = 0.017)。与那些GSTM1基因型不佳的亚洲患者相比,具有良好GSTM1基因型无效的亚洲患者对铂类化疗的反应率更高(OR = 1.493(1.192-1.870),P <0.001)。携带GSTT1空基因型的白种人肺癌患者可能比现存的GSTT1患者更短的生存时间和更高的死亡风险(危险比(HR)= 1.423,CI = 1.084-1.869,P = 0.011)。我们的荟萃分析表明,GSTP1 IIe105Val,GSTM1和GSTT1无效变体可能是铂类化学疗法对NSCLC患者疗效的预测因素。 GSTP1 IIe105Val,GSTM1和GSTT1无效多态性作为NSCLC患者个性化铂类化疗疗效的预测因素的使用,需要通过多中心,多种族和大样本量的药物遗传学研究进行进一步验证。

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