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谷胱甘肽S-转移酶T1(GSTT1)、谷胱甘肽S-转移酶P1(GSTP1)和谷胱甘肽S-转移酶M1(GSTM1)基因变异与既往未经治疗的转移性乳腺癌患者的生存率相关。

GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer.

作者信息

Zhang Jian, Wu Ying, Hu Xichun, Wang Biyun, Wang Leiping, Zhang Sheng, Cao Jun, Wang Zhonghua

机构信息

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

出版信息

Oncotarget. 2017 Nov 14;8(62):105905-105914. doi: 10.18632/oncotarget.22450. eCollection 2017 Dec 1.

Abstract

PURPOSE

The polymorphisms in genes including GSTM1, GSTP1 and GSTT1 have been found to predict development and therapeutic efficacy in various malignancies. Breast cancer is one of most common cancers among women. In this study, we evaluated the prognostic value of three functional polymorphisms of GSTs in patients with previously untreated metastatic breast cancer (MBC).

PATIENTS AND METHODS

The genotype of GSTT1, GSTP1, and GSTM1 in 170 patients with previously untreated MBC from one single center were assessed via PCR-based RFLP methods. The prognostic of polymorphisms on overall survival (OS) was examined using the Kaplan-Meier estimates and Cox proportional hazard ratio (HR) regression analyses.

RESULTS

The null genotypes of GSTT1 and GSTM1 were significantly correlated to poor OS compared with the present genotypes, respectively. After adjusting for clinic-pathologic factors, GSTT1 and GSTM1 genetic variants were still significantly associated with OS (HR, 1.92; 95% CI, 1.26-2.91 and HR, 1.53; 95% CI, 1.05-2.23). GSTT1 and GSTM1 were independent survival predictors and GSTP1 was not associated with overall survival of previous untreated MBC.

CONCLUSION

This exploratory analysis suggests that in addition to clinic-pathologic factors, the genetic variants in GSTT1 and GSTM1 might be predictive of survival outcome in patients with previously untreated MBC.

摘要

目的

已发现包括GSTM1、GSTP1和GSTT1在内的基因多态性可预测各种恶性肿瘤的发生发展及治疗效果。乳腺癌是女性中最常见的癌症之一。在本研究中,我们评估了谷胱甘肽S-转移酶(GSTs)的三种功能多态性对先前未经治疗的转移性乳腺癌(MBC)患者的预后价值。

患者与方法

采用基于聚合酶链反应(PCR)的限制性片段长度多态性(RFLP)方法,对来自单一中心的170例先前未经治疗的MBC患者的GSTT1、GSTP1和GSTM1基因型进行评估。使用Kaplan-Meier估计法和Cox比例风险比(HR)回归分析来检验多态性对总生存期(OS)的预后影响。

结果

与现有基因型相比,GSTT1和GSTM1的无效基因型分别与较差的OS显著相关。在调整临床病理因素后,GSTT1和GSTM1基因变异仍与OS显著相关(HR,1.92;95%可信区间[CI],1.26 - 2.91和HR,1.53;95%CI,1.05 - 2.23)。GSTT1和GSTM1是独立的生存预测因子,而GSTP1与先前未经治疗的MBC的总生存期无关。

结论

这项探索性分析表明,除临床病理因素外,GSTT1和GSTM1的基因变异可能预测先前未经治疗的MBC患者的生存结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/5739688/344bfe732625/oncotarget-08-105905-g001.jpg

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