Background: Glutathione S-transferase (GST) pi (GSTP1) is a detoxification enzyme with substrate specificity for both exogenous carcinogens and chemotherapy agents. Genetic polymorphisms of GSTP1 exon 5 (Ile105Val) and exon 6 (Ala114Val) appear to reduce this enzyme's activity. Previously, the authors reported that the exon 6 variant was associated with an increased risk of lung carcinoma, particularly among men, younger patients, and ever smokers. In this study, the authors hypothesized that variant GSTP1 genotype would result in reduced inactivation of chemotherapy agents and improved survival in patients with advanced-stage nonsmall cell lung carcinoma (NSCLC), a population that is likely to receive platinum-based chemotherapy.
Methods: Patients with Stage III and IV NSCLC who were enrolled in a molecular epidemiology study were identified, and a polymerase chain reaction-restriction fragment length polymorphism assay was used to genotype GSTP1 exons 5 and 6 in 424 patients and 425 patients, respectively.
Results: Patients who had the exon 6 variant genotype (Ala/Val or Val/Val) had significantly better survival compared with patients who had the wild type genotype (Ala/Ala; P = 0.037), with median survival of 16.1 months and 11.4 months, respectively. Multivariate analysis revealed a reduced adjusted hazard ratio (HR) of death associated with the exon 6 variant genotype of 0.75 (95% confidence interval [95% CI], 0.54-1.05). This protective association was observed in younger patients (younger than age 62 yrs; HR, 0.59; 95% CI, 0.57-0.97) and in males (HR, 0.64; 95% CI, 0.41-0.99). GSTP1 exon 5 genotype was not associated with survival.
Conclusions: GSTP1 exon 6 variant genotypes may be associated with improved survival among patients with Stage III and IV NSCLC.