INCREASED RISK FOR MYELODYSPLASTIC SYNDROMES IN INDIVIDUALS WITH GLUTATHIONE-TRANSFERASE-THETA-1 (GSTT1) GENE DEFECT

Background The glutathione S-transferases (GST) mediate exposure to va rious cytotoxic and genotoxic agents, including those associated with increased risk of the myelodysplastic syndromes (MDS). Both GST M1 (GS TM1) and GST theta 1 (GSTT1) genes have a ''null'' variant allele, in which the entire gene is absent. We tested whether the homozygous null genotype of GSTM1 and GSTT1 altered the risk for MDS. Methods In a ho spital-based case-control study we analysed lymphocyte or bone-marrow DNA samples from 96 patients with MDS and 201 cancer-free controls of similar, age, race, and sex. We have restricted our report to the 92 w hite MDS patients. We analysed GSTM1 and GSTT1 genotypes by PCR. Findi ngs The frequency of the GSTT1 null genotype was higher among MDS case s (46%) than among controls (16%). Inheritance of the GSTT1 null genot ype conferred a 4.3-fold risk of MDS (odds ratio 4.3, 95% CI 2.5-7.4, p<0.00001). The GSTM1 null genotype was not associated with increased risk of MDS (odds ratio 0.8, 0.5-1.3). Interpretation Individuals with the GSTT1 null genotype may have enhanced susceptibility to MDS. The mechanism might involve decreased detoxification of environmental or e ndogenous carcinogens.