title: Glutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung cancer patients.
abstract: 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 Ile(105)Val 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.
authors.affiliation: Division of Epidemiology, University of Minnesota, Minneapolis, Minnesota 55454, USA. sweeney@epi.umn.edu
authors.forename: Carol
authors.initials: C
authors.lastname: Sweeney
authors.forename: Valle
authors.initials: V
authors.lastname: Nazar-Stewart
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Stapleton
authors.forename: David L
authors.initials: DL
authors.lastname: Eaton
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*; D016016:Proportional Hazards Models; D012907:Smoking / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D013223:Statistics as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D014861:Washington / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human