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谷胱甘肽S-转移酶基因多态性在乳腺癌预后中的预测潜在作用。

Predictive potential role of glutathione S-transferase polymorphisms in the prognosis of breast cancer.

作者信息

Wang X, Huang Z H

机构信息

Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Genet Mol Res. 2015 Aug 28;14(3):10236-41. doi: 10.4238/2015.August.28.7.

DOI:10.4238/2015.August.28.7
PMID:26345960
Abstract

The current study aimed at evaluating the associa-tion between GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms and clinical response to chemotherapy and treatment outcome of breast cancers patients. Genotyping of GSTP1 rs1695, GSTT1 deletion, and GSTM1 deletion was performed by Polymerase Chain Reaction Restriction Fragment Length Polymor-phism (PCR-RFLP) assay. We found that patients with GG genotype of GSTP1 IIe105Val and null genotype of GSTM1 were more likely to have a poorer response to chemotherapy than homozygotes of the most frequent genotype; the ORs(95%CI) were 0.37(0.18-0.74) and 0.59(0.36-0.97), respectively. By the Cox proportional hazards model, patients with the GG genotype of GSTP1 IIe105Val and null genotype of GSTM1 were found to be correlated with shorter overall survival of breast cancer; the adjusted HR (95%CI) were 2.51(1.17-5.32) and 2.00(1.15-3.48), respectively. Thus, our findings provided statistical evidence that the variants of GSTP1 and GSTM1 polymorphisms could influence the response to chemotherapy and overall survival in breast cancer patients treated with chemotherapy.

摘要

本研究旨在评估谷胱甘肽S-转移酶M1(GSTM1)缺失/存在、谷胱甘肽S-转移酶T1(GSTT1)缺失/存在以及谷胱甘肽S-转移酶P1(GSTP1)Ile105Val多态性与乳腺癌患者化疗临床反应及治疗结局之间的关联。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法对GSTP1 rs1695、GSTT1缺失和GSTM1缺失进行基因分型。我们发现,GSTP1 Ile105Val的GG基因型和GSTM1的缺失基因型患者比最常见基因型的纯合子对化疗的反应更差;比值比(ORs)(95%置信区间)分别为0.37(0.18 - 0.74)和0.59(0.36 - 0.97)。通过Cox比例风险模型发现,GSTP1 Ile105Val的GG基因型和GSTM1的缺失基因型患者与乳腺癌患者较短的总生存期相关;调整后的风险比(HR)(95%置信区间)分别为2.51(1.17 - 5.32)和2.00(1.15 - 3.48)。因此,我们的研究结果提供了统计学证据,表明GSTP1和GSTM1多态性变体可影响接受化疗的乳腺癌患者的化疗反应和总生存期。

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