Polymorphisms in the GST (M1 andT1) gene and their possible association with susceptibility to childhood acute lymphocytic leukemia in Indian population

Abstract

Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of several environmental mutagens, carcinogens and anticancer drugs. GST polymorphisms resulting in decreased enzymatic activity have been associated with several types of solid tumors. We determined the frequencies of the deletion of two GST subfamilies genes, M1 and T1, in patients with acute lymphocytic leukemia (ALL). Using polymerase chain reactions, we analyzed the GSTM1 and GSTT1 genotype in 135 patients with ALL (01-10 years) and 146 age matched controls. The prevalence of GSTM1 and GSTT1 homozygous resulting in null genotypes at the GSTM1 and GSTT1 loci were detected 60 (44.44%) and 48 (35.55%) patients, and 61 (41.75%) and 23 (15.75%) controls, respectively. The presence of at least one GST
deletion proved to be an independent prognostic risk factor for response to treatment. In conclusion, individuals with GSTM1 or GSTT1 deletions (or deletions of both) may have an enhanced resistance to chemotherapy and a shorter survival