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

¹ Laboratorium voor Cellulaire Genetica and ² Laboratorium voor Antropogenetica, Vrije Universiteit Brussel, Brussels, Belgium; ³ Université catholique de Louvain, Unité de Toxicologie industrielle et Médecine du Travail, Brussels, Belgium; ⁴ Errol Zeiger Consulting, Road Chapel Hill, North Carolina; ⁵ Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy; ⁶ School of Public Health, University of California, Berkeley, California; ⁷ Institute of Environmental Health Sciences, National Yang Ming University Medical School, Taipei, Taiwan, Republic of China; ⁸ Laboratorium voor Arbeidshygiëne en-Toxicologie, Katholieke Universiteit Leuven, Leuven, Belgium; ⁹ Department of Public Health, Yamagata University Graduate School of Medicine, Yamagata, Japan; ¹⁰ Unidad de Toxicologia, Dpto. De Psicologia, Universidade da A Coruña, Edificio de Servicios Centrales de Investigación, A Coruña, Spain; ¹¹ Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Ciènces, Universitat Autònoma de Barcelona, Bellaterra, Spain; ¹² Dipartimento di Scienze dell'Uomo e dell' Ambiente e del Territorio, Università di Pisa, Pisa, Italy; ¹³ Laboratory of Molecular and Cellular Toxicology, Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland; ¹⁴ NIH, Environmental Health and Toxicology Department, Porto, Portugal; ¹⁵ Instituto Superiore di Sanità, Rome, Italy; and ¹⁶ CSIRO Health Sciences and Nutrition, Adelaide, South Australia, Australia

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

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)

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