An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma

Authors

  • David P. Miller ScD,

    1. Department of Environmental Heath, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts
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    • Dr. Miller was supported by a Flight Attendants Medical Research Institute Young Clinical Scientist Award.

  • Kofi Asomaning MBChB, MS,

    1. Department of Environmental Heath, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts
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  • Geoffrey Liu MD,

    1. Department of Environmental Heath, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts
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  • John C. Wain MD,

    1. Thoracic Surgery Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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  • Thomas J. Lynch MD,

    1. Oncology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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  • Donna Neuberg ScD,

    1. Department of Biostatistics, Harvard School of Public Health, Dana-Farber Cancer Institute, Boston, Massachusetts
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  • Li Su BS,

    1. Department of Environmental Heath, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts
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  • David C. Christiani MD

    Corresponding author
    1. Department of Environmental Heath, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts
    2. Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
    • Harvard School of Public Health, 665 Huntington Avenue, Building 1, Room 1402, Boston, MA 02115
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    • Fax: (617) 432-3441


Abstract

BACKGROUND.

Among the genes that encode the glutathione S-transferase (GST) superfamily of Phase 2 metabolizing enzymes, GSTP1 has the highest expression in the lung. The polymorphic GSTP1 gene encodes glutathione S-transferase π, which is an enzyme that detoxifies cigarette carcinogens, such as benzo-[a]-pyrene. The variant GSTP1 GG genotype is associated with lower enzymatic activity and higher DNA adduct levels in human lymphocytes compared with the AA genotype.

METHODS.

The authors evaluated the association of GSTP1 genotypes with lung cancer in 1921 cases and 1343 controls of Caucasian descent by using polymerase chain reaction-restriction fragment length polymorphism techniques. The results were analyzed with multiple logistic regression adjusting for age, gender, smoking status, and pack-years. To investigate specifically the subset of younger lung cancer patients and controls, the effect of age (either as a dichotomous or continuous variable in separate models) was analyzed as a modifying factor of the association between the GSTP1 polymorphism and lung cancer.

RESULTS.

The GSTP1 GG genotype was not associated with an overall increased risk of lung cancer (adjusted odds ratio, 1.02; 95% confidence interval [95% CI], 0.78–1.34) compared with the GSTP1 AA genotype. In both models that evaluated the gene-age interaction, an overall statistically significant interaction (P < .01) was observed between age and the GG genotype. However, for the model that included age as a dichotomous variable, the odds ratio of lung cancer risk with the GG genotype compared with the AA among individuals age ≤50 years was 2.67 (95% CI, 1.36–5.22); in older individuals, the risk was 0.87 (95% CI, 0.65–1.2).

RESULTS.

The GSTP1 GG genotype was associated with increased lung cancer susceptibility among younger study participants. Cancer 2006. © 2006 American Cancer Society.

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