Increased risk for acute myeloid leukaemia in individuals with glutathioneS-transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defects

Objectives: Glutathione S-transferases (GST) modulate the effects of exposu re to various cytotoxic and genotoxic agents, including those associated wi th increased risks of the myelodysplastic syndrome (MDS), acute myeloid leu kaemia (AML) and aplastic anemia (AA). Both the GST mu 1 (GSTM1) and GST th eta 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 G STT1 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 wit h AML (26.3% compared with 5.0% in the controls). In contrast, no differenc es in the frequencies of the null genotypes were found among MDS patients, AA patients and the controls. Conclusion: 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 wi th the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6-fold (95% Cl : 2.4-7.9) increased risk associated with the combined null genotype presen ts preliminary evidence that the inherited absence of this carcinogen detox ification pathway may be an important determinant of AML.