Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Cancer. 2010 May 1;116(9):2242-9. doi: 10.1002/cncr.25006.
Glutathione S-transferases (GSTs) are polymorphic enzymes that are responsible for glutathione conjugation of alkylators and scavenging of free radicals created by radiation. GST polymorphisms may result in altered or absent enzyme activity and have been associated with survival in patients with cancer. The authors of this report hypothesized that patients with anaplastic glioma (AG) who have GST genotypes that encode for lower activity enzymes will have longer survival than similar patients who have higher activity genotypes. The current study was performed to investigate the role of GST enzyme polymorphisms in predicting the survival of patients with AG.
The medical records of 207 patients with AG from a single cancer center were reviewed retrospectively. Polymorphisms for the GST micro1 (GSTM1), GST theta1 (GSTT1), and GST pi1 (GSTP1) enzymes were identified. Overall survival was compared using the Kaplan-Meier method and Cox proportional hazards analyses adjusting for age, sex, histology, and therapy.
Among the patients with oligodendroglial tumors (n = 94), patients who had the GSTT1 null genotype had a 2.9 times increased risk of death (95% confidence interval [CI], 1.3-6.3) compared with patients who had the GSTT1 non-null genotype. Adjustment for 1p/19q status did not change the finding. In the patients who had anaplastic astrocytoma (n = 113), the patients with all GSTP1 genotypes except GSTP1 *B/*B had a 3.8 times increased risk of death (95% CI, 0.5-29.6) compared with patients who had the GSTP1 *B/*B genotype.
In patients with anaplastic oligodendroglial tumors, the GSTT1 null genotype may be associated with poor survival, possibly because of modifications in therapy secondary to increased toxicity. This hypothesis is under investigation. In patients with anaplastic astrocytoma, the GSTP1 *B/*B genotype may confer a survival advantage.
谷胱甘肽 S-转移酶（GSTs）是多态酶，负责烷基化剂的谷胱甘肽结合和辐射产生的自由基清除。GST 多态性可能导致酶活性改变或缺失，并与癌症患者的生存相关。本文作者假设，具有编码低活性酶的 GST 基因型的间变性神经胶质瘤（AG）患者的生存时间将长于具有更高活性基因型的相似患者。目前的研究旨在探讨 GST 酶多态性在预测 AG 患者生存中的作用。
回顾性分析了来自单一癌症中心的 207 例 AG 患者的病历。鉴定了 GST 微 1（GSTM1）、GST theta1（GSTT1）和 GST pi1（GSTP1）酶的多态性。使用 Kaplan-Meier 方法和 Cox 比例风险分析比较总生存率，调整年龄、性别、组织学和治疗因素。
在少突胶质细胞瘤患者（n=94）中，GSTT1 缺失基因型患者的死亡风险增加 2.9 倍（95%置信区间[CI]，1.3-6.3），而 GSTT1 非缺失基因型患者的死亡风险增加 2.9 倍。1p/19q 状态的调整并未改变这一发现。在间变性星形细胞瘤患者（n=113）中，除 GSTP1*B/B 外，所有 GSTP1 基因型患者的死亡风险增加 3.8 倍（95%CI，0.5-29.6），而 GSTP1B/*B 基因型患者的死亡风险增加 3.8 倍。
在间变性少突胶质细胞瘤患者中，GSTT1 缺失基因型可能与生存不良相关，可能是由于毒性增加导致治疗方式改变。这一假设正在研究中。在间变性星形细胞瘤患者中，GSTP1*B/*B 基因型可能具有生存优势。
