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首页> 外文期刊>Pharmacogenetics and genomics >Glutathione S-transferase polymorphisms in osteosarcoma patients.
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Glutathione S-transferase polymorphisms in osteosarcoma patients.

机译：骨肉瘤患者谷胱甘肽S-转移酶多态性。

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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 GSTM3*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.
机译：背景：骨肉瘤是儿童和青少年中最常见的恶性骨肿瘤。多药耐药性和不良的临床结果仍然是影响骨肉瘤患者的问题。谷胱甘肽S-转移酶超基因家族包括几个基因，这些基因编码参与许多异种生物物质（包括致癌物和抗癌药）解毒的酶。这些基因的多态性已经与癌症易感性和抗癌药耐药性相关。目的：本研究旨在调查80例骨肉瘤患者和160例正常对照者的GSTM1，GSTT1和GSTM3基因的基因型频率，以及这些多态性对骨肉瘤患者临床结局的影响。方法：采用多重PCR技术检测GSTM1和GSTT1缺失多态性，采用PCR-限制性片段长度多态性方法检测内含子6上3个碱基对的GSTM3缺失。结果：我们发现，GSTM1无效基因型与不良的临床结果相关，其特征是肺复发发生率增加[比值比（OR）= 2.71，P = 0.036]，而至少有一个GSTM1等位基因与良好的反应相关改善治疗效果和生存率（OR = 4.28，P = 0.020，危险比= 4.09，P = 0.0078）。 GSTT1无效基因型与更好的总生存率相关（危险比= 7.15，P = 0.0247），而GSTM3 * B等位基因与诊断时的转移相关（OR = 2.83，P = 0.028）。结论：这项研究的结果表明，GST基因多态性可能与治疗反应和骨肉瘤的进展有关。

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