An Association Between Glutathione S-Transferase P1 Gene Polymorphism and Younger Age at Onset of Lung Carcinoma

Details

• Personal Author:
  Asomaning K ; Christiani, David C. ; Liu G ; Lynch TJ ; Miller DP ; Neuberg D ; Su L ; Wain JC
• Description:
  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 pi, 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). Conclusions: The GSTP1 GG genotype was associated with increased lung cancer susceptibility among younger study participants. [Description provided by NIOSH]
• Subjects:
  Aging Blood Carcinogens Energy Metabolism Enzymes Genetics Lung Lung Diseases Men Neoplasms Occupational Health Race Factors Respiratory System Respiratory Tract Diseases Safety Smokers Tobacco Products Women

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• Keywords:
  Age Groups Author Keywords: GSTP1 B(a)P Benzo(a)pyrene Case Control Cigarette Smoking DNA Adducts Early Age Onset Lung Carcinoma Genes Genotype Humans Interaction Logistic Regression Lung Cancer Lymphocytes Metabolism Models Racial Factors Statistical Analysis

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• ISSN:
  0008-543X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  107
• Issue:
  7
• NIOSHTIC Number:
  nn:20058611
• Citation:
  Cancer 2006 Oct; 107(7):1570-1577
• Contact Point Address:
  David C. Christiani, MD, Harvard School of Public Health, 665 Huntington Avenue, Building 1, Room 1402, Boston, MA 02115
• Email:
  christi@hsph.harvard.edu
• CAS Registry Number:
  Benzo[a]pyrene (CAS RN 50-32-8) ; Glutathione (CAS RN 70-18-8)
• Federal Fiscal Year:
  2007
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Cancer
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5483f6b8099ddada71f957a8a17df7fa970e2cbd7f11ff9536ca1593ce4226963439f1547e95ef9b392ec319919d398559e1100aa3793f303db81e6bfd3e492c
• Download URL:
  https://stacks.cdc.gov/view/cdc/221655/cdc_221655_DS1.pdf
• File Type:
  [PDF - 102.67 KB ]