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Glutathione S-transferase M1, T1, and P1 Polymorphisms and Survival among Lung Cancer Patients¹

Division of Epidemiology, University of Minnesota, Minneapolis, Minnesota 55454 [C. S.]; Center for Research on Environmental and Occupational Toxicology, Oregon Health and Science University, Portland, Oregon [V. N-S.]; Departments of Environmental Health [P. L. S., D. L. E.] and Epidemiology [T. L. V.], University of Washington, Seattle, Washington; and Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington [T. L. V.]

Glutathione S-transferase (GST) enzymes detoxify therapeutic drugs and reactive oxidants, so GST polymorphisms may influence survival after diagnosis of cancer. We evaluated survival according to GST polymorphisms in a population-based series of lung cancer patients. The study subjects (n = 274) were men diagnosed with lung cancer from 1993 through 1996 who participated in a case control study and provided a blood sample for genotyping. The presence of the GSTM1 and GSTT1 genes were assayed by multiplex PCR. Genotype at the GSTP1 Ile¹⁰⁵Val substitution was determined by PCR and oligonucleotide ligation assay. The study subjects were followed for vital status through 2000, and overall survival was evaluated in Kaplan-Meier survival functions and Cox proportional hazards models. Subjects with the GSTM1 null genotype had shorter survival; the proportion of GSTM1 null subjects surviving at 5 years was 0.20 [95% confidence interval (CI) 0.14–0.27], compared with 0.29 (95% CI 0.22–0.37) for GSTM1 present subjects. The relative risk of death associated with GSTM1 null genotype, adjusted for stage at diagnosis and histology, was 1.36, 95% CI 1.04–1.80. There was no association between GSTT1 or GSTP1 genotype and survival in the overall study population, nor in a subgroup of patients treated with chemotherapy (n = 130). For GSTM1, our results are consistent with a previous study, which also observed that the GSTM1-null genotype, which confers susceptibility to lung cancer, was associated with shorter survival. Future studies of lung cancer survival should take into account GSTM1 genotype as well as investigate underlying mechanisms.

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