Glutathione S transferase theta 1 gene defects in myelodysplastic syndromes and their correlation with karyotype and exposure to potential carcinogens

Abstract

Glutathione S transferase theta 1 (GSTT₁) is implicated in the detoxification of different substances, including carcinogens. Recently, an increased incidence of GSTT₁ null genotype was found in myelodysplastic syndromes (MDS) by comparison with a control population. We analyzed GSTT₁ gene by PCR in 174 MDS cases and 100 controls. The incidence of GSTT₁ null genotype was 22% in MDS in 19% in controls (P = 0.53). The incidence of GSTT₁ null genotype in MDS did not differ according to gender, FAB classification, karyotype and whether MDS were therapy related or ‘de novo’. In 86 of the de novo cases, data on previous occupational and environmental exposure to a list of 170 substances were available. In those MDS patients, a significantly lower frequency of GSTT₁ null genotype was seen in cases with previous jobs exposed to chemicals, and with previous exposure to mineral dusts and exhaust gases. A lower frequency (but with only borderline significance) was seen in MDS patients who had been coal miners and those who had been exposed to any of the 70 substances analyzed. Overall, GSTT₁ null genotype occurred at a similar incidence (19%) in controls and in MDS cases previously exposed to any substance, but tended to be higher in unexposed MDS patients (40%, P = 0.07). Our results do not confirm the higher incidence of GSTT₁ null genotype observed in MDS. The lower incidence of GSTT₁ null genotype in MDS cases exposed to some compounds previously found associated with MDS is apparently unexpected. However, it could be explained by the fact that GSTT₁ enzyme, which has a detoxification role for some compounds, could also have an activating role for other substances, including solvents.