Increased prevalence of GSTM(1) null genotype in patients with myelodysplastic syndrome: A case-control study

Background and Objective: Myelodysplastic syndromes (MDS) are clonal disord ers of bone marrow stem cells characterized by ineffective hematopoiesis le ading to blood cytopenia; they often progress to acute myeloid leukemia (AM L). The glutathione S-transferases (GST) detoxify various agents, including those implicated in MDS. Both GSTM(1) and GSTT(1) genes have 'null' allele s and are polymorphic. We studied the impact of GTM(1) and GSTT(1) null gen otypes on the MDS susceptibility, disease severity and laboratory indices w ith prognostic value for the syndrome. Material and Methods: In a hospital- based case-control study we analyzed lymphocyte DNA samples from 54 patient s with MDS and 60 cancer-free controls matched for age, sex, smoking habits and origin. A multiplex polymerase chain reaction was used to genotype bot h GSTM(1) and GSTT(1) simultaneously. The chi (2) test was used for statist ical evaluation of the data and the odds ratios and attributable risk and p opulation attributable risk were also calculated. Results: A significantly increased frequency of GSTM(1) null genotype was found among MDS patients ( 57.4%) compared to controls (33.3%) (p < 0.01), while the frequency of GSTT (1) null genotype was not significantly higher in MDS patients (11.1% vs. 6 .66%). Neither GSTM(1) and GSTT(1) null genotype was associated with a part icular category of the French-American-British (FAB) classification in the patients studied. Additionally, GSTM(1) null genotype was associated with a significant decrease in the absolute number of neutrophils among the MDS p atients. Conclusions: Individuals with GSTM(1) null genotype may have incre ased susceptibility to MDS. Null genotypes do not seem to have be associate d with FAB classification while they may be associated with putative progno stic factors. Copyright (C) 2001 S. Karger AG, Basel.