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Glutathione S-transferase polymorphisms in osteosarcoma patients

Carolina Salinas-Souza1, Antonio S Petrilli, Silvia R C de Toledo

  • 1Department of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC/UNIFESP), Genetics Laboratory, Federal University of São Paulo, São Paulo, Brazil.

Pharmacogenetics and Genomics
|June 26, 2010
PubMed
Abstract

Insights

Glutathione S-transferase (GST) gene polymorphisms influence osteosarcoma outcomes. Specific GSTM1 and GSTT1 genotypes correlate with treatment response, survival, and metastasis risk in osteosarcoma patients.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Osteosarcoma, a common pediatric bone cancer, faces challenges with multidrug resistance and poor outcomes.
  • Glutathione S-transferase (GST) enzymes are crucial for detoxifying xenobiotics, including chemotherapy drugs.
  • Genetic variations (polymorphisms) in GST genes are linked to both cancer development and drug resistance.

Purpose of the Study:

  • To determine the genotype frequencies of GSTM1, GSTT1, and GSTM3 genes in osteosarcoma patients and healthy controls.
  • To evaluate the impact of these GST gene polymorphisms on the clinical outcomes of osteosarcoma patients.

Main Methods:

  • Multiplex-PCR was used to analyze deletion polymorphisms in GSTM1 and GSTT1 genes.
  • PCR-restriction fragment length polymorphism (PCR-RFLP) identified a three-base pair deletion polymorphism in GSTM3 intron 6.

Main Results:

  • GSTM1 null genotype correlated with increased lung relapse (OR=2.71, P=0.036).
  • Presence of a GSTM1 allele was linked to better treatment response and survival (OR=4.28, P=0.020; HR=4.09, P=0.0078).
  • GSTT1 null genotype was associated with better overall survival (HR=7.15, P=0.0247), and GSTM3*B allele with metastasis at diagnosis (OR=2.83, P=0.028).

Conclusions:

  • GST gene polymorphisms may play a significant role in predicting treatment response in osteosarcoma.
  • These genetic variations could influence the progression and prognosis of osteosarcoma.

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