Increased risk for acute myeloid leukaemia in individuals with glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defects.
OBJECTIVE
Glutathione S-transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and aplastic anemia (AA). Both the GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. In this study, we tested whether null genotypes for the GSTM1 and GSTT1 genes altered the risks for MDS, AML and AA.


METHODS
Genomic DNA from 49 MDS, 38 AML and 37 AA patients and 276 controls was analysed using the polymerase chain reaction (PCR).


RESULTS
The frequencies of GSTM1 (73.6%) and GSTT1 (34.2%) null genotypes were significantly higher in AML patients than in the controls (36.9 and 18.1%, respectively). A higher frequency of the combined null genotype for both genes was also observed in patients with AML (26.3% compared with 5.0% in the controls). In contrast, no differences in the frequencies of the null genotypes were found among MDS patients, AA patients and the controls.


CONCLUSIONS
Our observation of a 4.7-fold (95% CI: 2.1-11.0) and 2.3-fold (95% CI: 1.0-5.2) increased risk associated with the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6-fold (95% CI: 2.4-7.9) increased risk associated with the combined null genotype presents preliminary evidence that the inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.
Arruda
V R
VR
Department of Internal Medicine, State University of Campinas, Campinas, São Paulo, Brazil.
Lima
C S
CS
Grignoli
C R
CR
de Melo
M B
MB
Lorand-Metze
I
I
Alberto
F L
FL
Saad
S T
ST
Costa
F F
FF
D000208:Acute Disease; D000328:Adult; D000483:Alleles; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D015386:Hazardous Substances / Q000009:adverse effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D012307:Risk Factors
D005982:Glutathione Transferase; D015386:Hazardous Substances; C413545:glutathione S-transferase T1