The Effects of GSTM1 and GSTT1 Polymorphisms on Micronucleus Frequencies in Human Lymphocytes In vivo

  1. Micheline Kirsch-Volders1,
  2. Raluca Antonina Mateuca1,
  3. Mathieu Roelants2,
  4. Annie Tremp1,
  5. Errol Zeiger4,
  6. Stefano Bonassi5,
  7. Nina Holland6,
  8. Wushou Peter Chang7,
  9. Peter Vande Aka1,
  10. Marlies DeBoeck1,
  11. Lode Godderis8,
  12. Vincent Haufroid3,
  13. Hitoshi Ishikawa9,
  14. Blanca Laffon10,
  15. Ricardo Marcos11,
  16. Lucia Migliore12,
  17. Hannu Norppa13,
  18. Joao Paulo Teixeira14,
  19. Andrea Zijno15 and
  20. Michael Fenech16
  1. 1Laboratorium voor Cellulaire Genetica and 2Laboratorium voor Antropogenetica, Vrije Universiteit Brussel, Brussels, Belgium; 3Université catholique de Louvain, Unité de Toxicologie industrielle et Médecine du Travail, Brussels, Belgium; 4Errol Zeiger Consulting, Road Chapel Hill, North Carolina; 5Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy; 6School of Public Health, University of California, Berkeley, California; 7Institute of Environmental Health Sciences, National Yang Ming University Medical School, Taipei, Taiwan, Republic of China; 8Laboratorium voor Arbeidshygiëne en-Toxicologie, Katholieke Universiteit Leuven, Leuven, Belgium; 9Department of Public Health, Yamagata University Graduate School of Medicine, Yamagata, Japan; 10Unidad de Toxicologia, Dpto. De Psicologia, Universidade da A Coruña, Edificio de Servicios Centrales de Investigación, A Coruña, Spain; 11Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Ciènces, Universitat Autònoma de Barcelona, Bellaterra, Spain; 12Dipartimento di Scienze dell'Uomo e dell' Ambiente e del Territorio, Università di Pisa, Pisa, Italy; 13Laboratory of Molecular and Cellular Toxicology, Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland; 14NIH, Environmental Health and Toxicology Department, Porto, Portugal; 15Instituto Superiore di Sanità, Rome, Italy; and 16CSIRO Health Sciences and Nutrition, Adelaide, South Australia, Australia
  1. Requests for reprints:
    Micheline Kirsch-Volders, Laboratory of Cell Genetics, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. Phone: 322-629-34-23; Fax: 322-629-27-59. E-mail: mkirschv{at}vub.ac.be

Abstract

The influence of genetic polymorphisms in GSTM1 and GSTT1 genes on micronucleus frequencies in human peripheral blood lymphocytes was assessed through a pooled analysis of data from seven laboratories that did biomonitoring studies using the in vivo cytokinesis-block micronucleus assay. A total of 301 nonoccupationally exposed individuals (207 males and 94 females) and 343 workers (237 males and 106 females) occupationally exposed to known or suspected genotoxic substances were analyzed by Poisson regression. The results of the pooled analysis indicate that the GSTT1 null subjects had lower micronucleus frequencies than their positive counterparts in the total population (frequency ratio, 0.55; 95% confidence interval, 0.33-0.89). The protective effect of this genotype is reversed with increasing age, with a frequency ratio of 1.33 (95% confidence interval, 1.06-1.68) in subjects aged 60 years. A significant overall increase in micronucleus frequency with age and gender (P < 0.001 and P = 0.024, respectively) was observed, females having higher micronucleus frequencies than males, when occupationally exposed (P = 0.002). Nonoccupationally exposed smokers had lower micronucleus frequencies than nonsmokers (P = 0.001), whereas no significant difference in micronucleus level was observed between smokers and nonsmokers in the occupationally exposed group (P = 0.79). This study confirms that pooled analyses, by increasing the statistical power, are adequate for assessing the involvement of genetic variants on genome stability and for resolving discrepancies among individual studies. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1038–42)

Footnotes

  • ↵17 L. Migliore, personal communication.

  • Grant support: European Union Project Cancer Risk Biomarkers contract QLK4-2000-00628 and the Belgian Federal Offices for Scientific, Technical, and Cultural Affairs of the Prime Minister's Service contract PS/03/35.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Note: M. Kirsch-Volders, R.A. Mateuca, M. Roelants, A. Tremp, E. Zeiger, S. Bonassi and M. Fenech are the main authors of the present article.

  • H. Norppa is the Coordinator of the Cancer Risk Biomarkers EU program on predictivity of cytogenetic biomarkers for cancer.

  • M. De Boeck, L. Godderis, V. Haufroid, B. Laffon, R. Marcos, L. Migliore, J. P. Teixeira, and A. Zijno contributed data to the pooled analysis.

  • M. De Boeck is currently at Johnson & Johnson Pharmaceutical Research and Development (a Division of Janssen Pharmaceutica n.v.), Genetic and In vitro Toxicology, Turnhoutseweg 30, B-2340 Beerse, Belgium.

    • Accepted March 2, 2006.
    • Received July 6, 2005.
    • Revision received February 14, 2006.
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  1. doi: 10.1158/1055-9965.EPI-05-0487 Cancer Epidemiology, Biomarkers & Prevention May 1, 2006 15, 1038
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