Association between glutathione S-transferase π polymorphisms and survival in patients with advanced nonsmall cell lung carcinoma

Authors

  • Charles Lu M.D.,

    Corresponding author
    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Thoracic/Head and Neck Medical Oncology, Unit 432, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009
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    • Fax: (713) 796-8655

    • Charles Lu is a recipient of the Clinical Oncology Research Career Development Award from the National Cancer Institute.

  • Margaret R. Spitz M.D., M.P.H.,

    1. Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Hua Zhao Ph.D.,

    1. Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Qiong Dong M.S.,

    1. Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Mylene Truong M.D.,

    1. Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Joe Y. Chang M.D.,

    1. Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • George R. Blumenschein Jr. M.D.,

    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Waun K. Hong M.D.,

    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Xifeng Wu M.D., Ph.D.

    1. Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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Abstract

BACKGROUND

Glutathione S-transferase (GST) π (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. Cancer 2006. © 2005 American Cancer Society.

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