The Association Between Polymorphisms in Glutathione S-Transferase (GSTM1 and GSTT1) and Lung Cancer Outcome

Abstract

Background: Polymorphisms in the glutathione S-transferase (GST) family may be associated with increased risk of lung cancer, somatic changes in lung tumour tissue, and survival. We evaluated survival according to GST polymorphism in lung cancer patients. Methods: We studied DNA polymorphisms of 81 primary lung cancer patients at 2 glutathione-related loci: GSTM1, and GSTT1 that encode glutathione S-transferase-μ, and glutathione S-transferase-□. The presences of the GSTM1 and GSTT1 genes were assayed by PCR. Kaplan-Meier with log rank tests, and Cox regression models were applied in the analysis. Results: The median age of 75 males and 6 females was 60 years. Median survival of the whole population was 8 months. In the first presentation, none of the patients with GSTT1 null genotype but 30 percent of the patients with GSTT1-positive genotype had liver metastasis (p < 0.01) but GSTT1 genotype was not associated with survival. Sputum (p < 0.01) was more common in patients with GSTM1 null genotype. Subjects with the GSTM1-null genotype had shorter survival. Using a Cox proportional hazard model, GSTM1, tumor (T) factor and thoracic irradiation status were identified as independent prognostic factors. Conclusions: Our preliminary results showed that GSTM1-null genotype was associated with shorter survival.

Keywords:

• Glutathione
• Metabolism
• Chemotherapy