GSTM1/GSTT1-null genotyping role in leukemia development in Brazilian patients

Glutathione S-transferases are detoxification enzymes that protect cells from oxidative stress and help maintain genomic integrity. GSTM and GSTT family genes may be deleted. causing reduced or no glutathione S-transferase activity so that electrophilic carcinogens cannot be eliminated efficiently. This genetic alteration affects cancer incidence and prognosis. We genotyped GSTM1 and GSTT1 in 87 Brazilian leukemia patients by multiplex PCR, divided into acute or chronic, and lymphocytic or myeloid type cancers. GSTM1-null and GSTT1-null frequency was significantly higher in chronicmyeloid leukemia (67.65% and 46.20%) and chroniclymphoid leukemia (29.41% and 12.30%) in relation to controls, respectively, than in non-leukemia controls. More than that, double null genotyping was significantly more present in acutelymphoid leukemia than controls. When individual GSTM1 and GSTT1 genotyping were analyzed, again CML and CLL presented significantly diferent in genotyping frequency compared to controls (11.11% and 3.8%). Double null genotypes were significantly more frequent in acute lymphoid leukemia than in controls. Furthermore, CML patients presented a statistically significant higher percentage of double-null and GSTM1-null genotypes, and CLL patients had a significantly higher frequency of GSTT1-null genotyping when compared to controls. We suggest that GST genotypes are an important risk factor for leukemia development in the Brazilian population, especially in chronic leukemia due to inefficient detoxification of oxidative stress products.

Automated summary

Deletion of GSTM1 and GSTT1 genes may cause reduced glutathione S-transferase activity, leading to increased risk of leukemia. The frequency of GSTM1-null and GSTT1-null genotypes was significantly higher in Brazilian leukemia patients, especially in chronic leukemia.