Conference Proceeding

Role of GSTM1 & GSTT1 gene polymorphism in susceptibility to acute lymphoblastic leukemia

Ms. Naveena Shri S,
Consultant, Global Health City

Acute lymphoblastic leukemia (ALL) characterized by proliferation of immature B or T cells in bone marrow, Lymphnodes, spleen & blood remains the leading cause of cancer related death in children. Many polymorphisms in the genes coding for xenoBiographytic metabolizing enzymes (XME) has been identified and studies have reported significant association with the gene variation and enzyme activity.

Background: Acute lymphoblastic leukemia (ALL) characterized by proliferation of immature B or T cells in bone marrow, Lymphnodes, spleen & blood remains the leading cause of cancer related death in children. Many polymorphisms in the genes coding for xenoBiographytic metabolizing enzymes (XME) has been identified and studies have reported significant association with the gene variation and enzyme activity. The inter -individual variations in the activity of XME could play a role in increasing susceptibility to ALL in pediatric age group. Glutathione Stransferases are enzymes involved in detoxification of several environment mutagen, carcinogens & anticancer drug. This study aims to explore the gene polymorphisms of Glutathione S-transferases (GSTM1 & GSTT1) on Indian children & their relationship with ALL susceptibility.
Method: The study included 50 cases of children (Aged 0-18yrs) diagnosed with ALL, and control of normal children (Aged 0-18yrs) Blood samples were collected, and genomic DNA was isolated and the GSTM1 and GSTT1 genotyping was performed using PCR based methodologies. The PCR products were analyzed using agarose gel electrophoresis. The results were interpreted based on the presence amplicon.
Results: Allele and genotype frequencies were determined by the gene counting method. Hardy Weinberg equilibrium was tested. The relationship between GSTM1 and GSTT1 genotypes and ALL was analyzed using the χ2 test. Reference genotypes/alleles were used to calculate crude odds ratios (ORs) and 95% confidence intervals (CIs). Logistic regression analysis was performed to correlate the age, stage and prognosis.
Discussion: The glutathione S-transferase mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) are phase II enzymes that have the ability to detoxify numerous electrophilic compounds including the activated carcinogens. Both GSTM1 and GSTT1 exhibit genetic polymorphism in populations with a large percentage of individuals displaying a homozygous deletion of the structural genes. Studies have reported contradictory results for associations between GSTM1 and GSTT1 and cancer predisposition. Conclusion: Children with acute lymphoblastic leukemia show higher percentage of deletion of GSTT1, when compare to the control group of normal children

Published: 11 May 2017