Glutathione S-transferase polymorphisms in osteosarcoma patients.
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.
Salinas-Souza
Carolina
C
Department of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC/UNIFESP), Genetics Laboratory, Federal University of São Paulo, São Paulo, Brazil.
Petrilli
Antonio S
AS
de Toledo
Silvia R C
SR
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
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C483009:GSTM3 protein, human