Lafuente A, Maristany M, Arias C, Cuchi A, Lafuente M J, Molina R, Ballesta A, Trasserra J
Institut de Salut Publica, Universitat de Barcelona, Spain.
Anticancer Res. 1998 Jan-Feb;18(1A):107-11.
The aim of the present study was to establish the risk of squamous cell carcinoma (SCC) of the larynx associated with the congenital absence of glutathione S-transferase M1 (GSTM1), and to describe the expression of the isoenzymes GSTA1/2, GSTP1-1, and GSTM1 and glutathione (GSH) content in healthy and tumoral larynx tissue.
Blood samples from 160 SCC male patients and 158 controls were phenotyped for GSTM1 by ELISA. Using 37 paired samples (normal and tumour specimens) from cancer patients we carried out a descriptive study of enzyme activity by ELISA (GSTs) and Ellman's as say (GSH) RESULTS: GSTM1 null phenotype was more common in the SCC group than in controls (OR 1.9, CIs 1.18-3.05, p = 0.004). Total GST activity was higher in tumour samples than in matched healthy tissue (2.2-fold, p-0.00001), being largely determined by GSTP1-1 (1.9-fold increased in malignant tissue; p = 0.0003). The GSH content was also significantly higher in SCC than in normal mucosa (1.9-fold, p = 0.0007).
We confirmed the GSTM1-dependent risk for larynx cancer among smokers. The overexpression of the GST/GSH system in tumours reported here indicates their possible role in chemoresistance to pharmacological therapy.
本研究旨在确定与谷胱甘肽S-转移酶M1（GSTM1）先天性缺失相关的喉鳞状细胞癌（SCC）风险，并描述健康和肿瘤喉组织中同工酶GSTA1/2、GSTP1-1和GSTM1的表达以及谷胱甘肽（GSH）含量。
通过酶联免疫吸附测定法（ELISA）对160例男性SCC患者和158例对照的血样进行GSTM1表型分析。利用来自癌症患者的37对样本（正常和肿瘤标本），通过ELISA（GSTs）和埃尔曼测定法（GSH）对酶活性进行描述性研究。结果：GSTM1无效表型在SCC组中比在对照组中更常见（比值比1.9，置信区间1.18 - 3.05，p = 0.004）。肿瘤样本中的总GST活性高于匹配的健康组织（2.2倍，p = 0.00001），这在很大程度上由GSTP1-1决定（恶性组织中增加1.9倍；p = 0.0003）。SCC中的GSH含量也显著高于正常黏膜（1.9倍，p = 0.0007）。
我们证实了吸烟者中存在GSTM1依赖性喉癌风险。此处报道的肿瘤中GST/GSH系统的过表达表明它们可能在对药物治疗的化疗耐药中发挥作用。
