The effects of GSTM1 and GSTT1 polymorphisms on micronucleus frequencies in human lymphocytes in vivo.
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.
Kirsch-Volders
Micheline
M
Laboratory of Cell Genetics, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. mkirschv@vub.ac.be
Mateuca
Raluca Antonina
RA
Roelants
Mathieu
M
Tremp
Annie
A
Zeiger
Errol
E
Bonassi
Stefano
S
Holland
Nina
N
Chang
Wushou Peter
WP
Aka
Peter Vande
PV
Deboeck
Marlies
M
Godderis
Lode
L
Haufroid
Vincent
V
Ishikawa
Hitoshi
H
Laffon
Blanca
B
Marcos
Ricardo
R
Migliore
Lucia
L
Norppa
Hannu
H
Teixeira
Joao Paulo
JP
Zijno
Andrea
A
Fenech
Michael
M
D000293:Adolescent; D000328:Adult; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D010575:Pesticides / Q000633:toxicity; D016012:Poisson Distribution; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012997:Solvents / Q000633:toxicity; D013343:Styrenes / Q000633:toxicity; D001335:Vehicle Emissions / Q000633:toxicity
D005982:Glutathione Transferase; D010575:Pesticides; D012997:Solvents; D013343:Styrenes; D001335:Vehicle Emissions; C413545:glutathione S-transferase T1