Association of Glutathione-S-Transferase M1, P1, and T1 Gene Polymorphisms with Treatment Response in Childhood Acute Lymphocytic Leukemia

April Grace Dion-Berboso,1,2 Ma. Melanie Liberty B. Alcausin,1,2
Carmencita D. Padilla,1,2 Pamela D. Fajardo1 and Catherine Lynn T. Silao1,2

1 Department of Pediatrics, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
2 Institute of Human Genetics, National Institutes of Health Philippines,
University of the Philippines Manila

 

There is still a strong need for new treatment strategies that will maintain remission and prolong survival in patients with acute lymphoblastic leukemia (ALL). The gluetathione-S-transferase (GST) enzymes, which are coded by highly polymorphic genes, have been associated with the risk of developing cancer and were found to regulate effect of cancer treatment drugs.

Objectives. The present study determines the association of GSTM1, GSTP1, and GSTT1 polymorphisms and treatment response in terms of occurence of adverse events and relapse in ALL in Filipino children.

Methods. This is a follow up study on the 2007 investigation done by Alcausin et al. which determined the association of the GST P1, M1, and T1 polymorphisms and occurence of ALL. Four-year follow-up data were available for 46 out of the 50 patients from January 2007 to May 2011. Odds ratios (OR) as measures of association of GST M1, P1 and T1 gene polymorphisms with treatment outcomes were estimated at 95% confidence interval.

Results. Results show a trend towards predisposition to elevation of liver enzymes in patients with GSTT1 and GSTP1 mutant genotypes showing an OR (95% CI) of 3.0 (0.29-31.2) and 3.83 (0.37-40.0), respectively. There is also a trend towards development of infection in patients with the GSTT1 null genotype with an OR (95% CI) of 2.0 (0.62-6.49). The presence of GSTM1 null genotype showed a trend towards protection from occurence of relapse basing on both crude and adjusted ORs, 0.58 (0.16-2.07) and 0.23 (0.05-1.20), respectively. However, these results are not statistically significant.

Keywords: gluetathione-S-transferase, acute lymphoblastic leukemia, gene polymorphisms, adverse events, relapse