Genetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with the clinical outcome of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy
Genetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with the clinical outcome of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy
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DOI：
10.3892/mmr.2013.1435
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发表时间：
2013-06-01
影响因子：
3.4
通讯作者：
Pan, Yao-Dong
中科院分区：
文献类型：
--
作者：
Liu, Yong-Ping;Ling, Yang;Pan, Yao-Dong
本研究的目的是确定特定的分子参数是否可以作为奥沙利铂（OXA）为基础的化疗，这是作为切除的胃癌辅助治疗的治疗结果和毒性的预测。在该研究中检查的所有胃癌患者均接受OXA/5-氟尿嘧啶化疗方案。采用TaqMan 5'核酸酶分析法和直接测序法检测某些铂相关基因的遗传多态性。根据每个基因型评估无复发生存期（RFS）、总生存期（OS）和毒性。在对最相关的临床变量进行调整后，切除修复交叉互补组1（ERCC 1）-118和X射线修复交叉互补蛋白1我们还证明，携带至少一种变异XRCC 1 Arg 399 Gln或谷胱甘肽S-转移酶pi 1（GSTP 1）的人，Ile 105 Val等位基因显著增加任何3级或4级血液学毒性的风险。特别是，携带至少一个变体GSTP 1 Ile 105 Val等位基因也与3级或4级胃肠道毒性和神经毒性的风险增加显著相关。我们的数据表明，携带ERCC 1 -118 C/C和XRCC 1 -399 A/G或A/A基因型的胃癌患者可能从接受OXA为基础的辅助化疗中获益，携带至少一种变异XRCC 1 Arg 399 Gln或GSTP 1 Ile 105 Val等位基因可能有助于OXA为基础的化疗相关药物不良反应的发生。
The aim of the present study was to determine whether specific molecular parameters may serve as predictors of treatment outcomes and toxicity of oxaliplatin (OXA)-based chemotherapy, which is used as an adjuvant treatment in resected gastric cancer. All gastric cancer patients examined in the study received an OXA/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms of certain platinum-related genes were determined by the TaqMan 5' nuclease assay and direct sequencing. Relapse-free survival (RFS), overall survival (OS) and toxicity were evaluated according to each genotype. Following adjustment for the most relevant clinical variables, excision repair cross-complimentary group 1 (ERCC1)-118 and X-ray repair cross-complementing protein 1 (XRCC1-399) demonstrated significant predictive value for RFS and OS. We also demonstrated that carrying at least one variant XRCC1 Arg399Gln or glutathione S-transferase pi 1 (GSTP1) Ile105Val allele significantly increased the risk of any grade 3 or 4 hematological toxicity. In particular, carrying at least one variant GSTP1 Ile105Val allele was also significantly correlated with an increased risk of grade 3 or 4 gastrointestinal toxicity and neurotoxicity. Our data suggested that gastric cancer patients harboring ERCC1-118 C/C and XRCC1-399 A/G or A/A genotypes may benefit from receiving OXA-based adjuvant chemotherapy, and carrying at least one variant XRCC1 Arg399Gln or GSTP1 Ile105Val allele may contribute to the occurrence of adverse drug effects associated with OXA-based chemotherapy.