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Synergistic effects of NAT2 slow and GSTM1 null genotypes on carcinogen DNA damage in the lung

Mi-Sun Lee1, Li Su, David C Christiani

  • 1Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
|May 27, 2010
PubMed
Abstract

Insights

Genetic variations in NAT2 and GSTM1 influence DNA adduct levels in lung cancer patients. The combined effect of GSTM1 null and NAT2 slow genotypes significantly increases DNA damage in lung tissue.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Polymorphisms in carcinogen-detoxifying enzymes like NAT2 and GSTM1 are implicated in cancer susceptibility.
  • Limited data exists on the relationship between NAT2/GST gene polymorphisms and DNA adduct burden in lung tissue.

Purpose of the Study:

  • To investigate the independent and combined effects of NAT2 and GST gene polymorphisms on DNA adduct formation in lung and blood of lung cancer patients.

Main Methods:

  • DNA adducts were quantified using the (32)P-postlabeling assay in lung and blood samples.
  • Multiple regression models analyzed the association between GST/NAT2 genotypes and DNA adduct levels, adjusting for confounders.

Main Results:

  • GSTM1 null genotype was associated with a 150.3% increase in lung adducts; NAT2 slow acetylator genotype showed a 73.9% increase.
  • No significant association was found with GSTT1 and GSTP1 polymorphisms.
  • Combined GSTM1 null and NAT2 slow genotypes exhibited a synergistic effect, increasing lung adducts by 295%.

Conclusions:

  • Increased DNA adduct levels in the lung are linked to GSTM1 null and NAT2 slow genotypes, both individually and in combination.
  • GSTM1 and NAT2 genotypes play a significant role in carcinogen-induced DNA adduct formation in lung tissue, acting independently and interactively.

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