title: Glutathione S-transferase polymorphisms in osteosarcoma patients.
abstract: BACKGROUND
  Osteosarcoma is the most common malignant bone tumor in children and adolescents. Multidrug resistance and poor clinical outcome are the problems that still affect osteosarcoma patients. The glutathione S-transferase supergene family includes several genes that encode enzymes involved in the detoxification of many xenobiotic agents, including carcinogens and anticancer drugs. The polymorphisms in these genes have already been associated both with cancer susceptibility and anticancer drugs resistance.
  
  
  OBJECTIVE
  This study aims to investigate the genotype frequencies of GSTM1, GSTT1 and GSTM3 genes in 80 osteosarcoma patients and 160 normal control participants, and also the influence of these polymorphisms in the clinical outcome of osteosarcoma patients.
  
  
  METHODS
  GSTM1 and GSTT1 deletion polymorphisms were examined through a multiplex-PCR and the GSTM3 polymorphism of three base pair-deletion at intron 6 using PCR-restriction fragments length polymorphism method.
  
  
  RESULTS
  We found that GSTM1 null genotype is correlated to poor clinical outcome characterized by the increased lung relapse occurrence [odds ratio (OR)=2.71, P=0.036], while the presence of at least one GSTM1 allele is associated with a good response to treatment and better survival (OR=4.28, P=0.020 and hazards ratio=4.09, P=0.0078, respectively). The GSTT1 null genotype was correlated with a better overall survival (hazards ratio=7.15, P=0.0247), whereas GSTM3*B allele was associated with metastasis at diagnosis (OR=2.83, P=0.028).
  
  
  CONCLUSIONS
  The findings of this study suggest that GST polymorphisms may have a role in treatment response and osteosarcoma progression.
authors.affiliation: Department of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC/UNIFESP), Genetics Laboratory, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Salinas-Souza
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Petrilli
authors.forename: Silvia R C
authors.initials: SR
authors.lastname: de Toledo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018450:Disease Progression; D004587:Electrophoresis, Agar Gel; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D012516:Osteosarcoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C483009:GSTM3 protein, human