Glutathione S-transferase polymorphisms in osteosarcoma patients

Glutathione S-transferase polymorphisms in osteosarcoma patients

Author Salinas-Souza, Carolina Autor UNIFESP Google Scholar
Petrilli, Antonio S. Google Scholar
Toledo, Silvia R. C. de Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
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.Objectives 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 GSTM* B allele was associated with metastasis at diagnosis (OR=2.83, P=0.028).Conclusion the findings of this study suggest that GST polymorphisms may have a role in treatment response and osteosarcoma progression. Pharmacogenetics and Genomics 20:507-515 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
Keywords genetic polymorphism
glutathione S-transferase
GSTM1
GSTM3
GSTT1
osteosarcoma
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grupo de Apoio ao Adolescente e a Crianc, a com Cancer (GRAACC/UNIFESP)
Date 2010-08-01
Published in Pharmacogenetics and Genomics. Philadelphia: Lippincott Williams & Wilkins, v. 20, n. 8, p. 507-515, 2010.
ISSN 1744-6872 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 507-515
Origin http://dx.doi.org/10.1097/FPC.0b013e32833caa45
Access rights Closed access
Type Article
Web of Science ID WOS:000279865400005
URI http://repositorio.unifesp.br/handle/11600/32795

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