Polymorphisms and Protein Expressions of Glutathione S-Transferase M1 and T1 in Non-Small Cell Lung Cancer.

Abstract

The deletion polymorphisms of glutathione S-transferase (GST) GSTM1 and GSTT1 genes result in the absence of the corresponding protein, which decreases the detoxification of carcinogens. Studies evaluating polymorphisms and protein expressions in the same patients are limited. Therefore, in this study, we aimed to investigate the association between polymorphisms and protein expressions of GSTM1 and GSTT1 in lung tissues of patients with non-small cell lung cancer (NSCLC). For protein expression and gene deletion studies, tumor and surrounding tumor free (normal) tissue of 33 patients with NSCLC were used. In paraffin-embedded tissues, immunohistochemistry was used to detect protein expressions, and multiplex polymerase chain reaction amplification was used to identify gene deletions. GSTM1 and GSTT1 protein expressions were not detected in patients with GSTM1 and GSTT1 gene deletions, whereas protein expressions were detected in lung tissues of all patients carrying GSTM1 and GSTT1 genes. The protein expression level of GSTT1 was 2.0-fold higher in tumors of patients lacking GSTM1 genes than those with GSTM1 genes (p=0.018). Protein expression of GSTM1 was statistically higher in tumor tissues than in normal tissues of patients with GSTM1 genes (p=0.001). These results show that a) there is an association between gene deletions and protein expressions of GSTM1 and GSTT1 in patients with NSCLC, b) in the absence of GSTM1 genes, enhancement of expression of GSTT1 in tumors is likely to show that GSTT1 increases its capacity to detoxify the toxic electrophiles in tumors, and c) GSTM1 protein expression is higher in tumors compared with normal lung tissues of patients with NSCLC.