X线交错互补修复基因多态性与晚期胃癌患者对DDP化疗疗效的相关性研究

Relationship between Polymorphism of X-ray Repair Cross-complementing Group 1(XRCC1) Genes and Clinical Outcome of Advanced Gastric Cancer Patients Treated with DDP-based Chemotherapy

目的:本研究旨在观察x线交错互补修复基因(XRCC1399)多态性与以DDP为基础的化疗方案治疗晚期胃癌的疗效间的关系。方法:收集经病理确诊的晚期胃癌59例。所有晚期胃癌病例化疗前抽取外周血,提取脱氧核糖核酸(DNA),用连接酶检测反应技术检测研究对象的XRCC1399基因型。所有患者经多西他赛(Docetaxel)+5-氟尿嘧啶(5-FU)+顺铂(DDP)联合方案化疗,化疗后观察疗效及其与XRCC1399基因多态性之间的关系。结果:59例晚期胃癌患者中,16例(27.12%)为A/A基因型,18例(30.51%)为G/A基因型,25例(42.37%)为G/G基因型。其中,4例完全缓解(CR),14例为部分缓解(PR),19例稳定(SD),22例进展(PD),总化疗有效率为30.51%。XRCC1399 A/A基因型患者的化疗有效率(68.75%)明显高于G/A基因型患者(22.23%),P<0.01,明显高于G/G基因型患者(12.0%),P<0.01。G/A基因型患者的化疗有效率与G/G基因型患者之间无显著性差异,P>0.05。结论:XRCC1399基因型对预测以DDP为基础的化疗方案治疗晚期胃癌的疗效具有较好的临床意义,XRCC1399 A/A基因型的晚期胃癌患者对以DDP为主的化疗方案较为敏感。

Objective： Gastric cancer is one of the most common malignant tumors. Chemotherapy is an important part of gastric cancer treatment, especially for advanced gastric cancer patients. Gene polymorphism can affect the metabolism, transportation, and target of medicine, resulting in individual differences. To find a biological marker to identify the patients who can get benefits from the treatment has become a big challenge： The aim of this study was to investigate the correlation between genetic polymorphisms of the X-ray repair cross-complementing group 1 （XRCC1） genes and the clinical outcome of advanced gastric cancer patients treated with DDP-based chemotherapy. Methods： A total of 59 patients pathologically diagnosed with advanced gastric cancer were collected. DNAs of peripheral blood leukocytes of these patients were obtained before chemotherapy and were analyzed for XRCC1399 genotypes by PCR-LDR method. Then all of the patients were treated with chemotherapy of DOCETAXEL combined with 5-FU and DDP. The relationship between the gene polymorphism XRCC1399 and therapeutic effect was investigated. Results： The frequencies of XRCC1399 genotype were analyzed. A/A was 27.12%, G/A was 30.51%, and GIG was 42.37%. The total response rate to chemotherapy was 30.51%. Four patients had complete response, 14 had partial response, 19 had stable disease and 22 had progressive disease. However, the response rate in patients with A/A genotype （68.75%） was significantly higher than that in patients with G/A genotype （22.23%） and those with GIG genotype （12.0%）, with a significant difference （P〈0.01）. No significant difference was found in response rate between patients with G/A genotype and patients with GIG Etenotype （P〉0.05）. Conclusion： XRCC1399 polymorphism can predict the therapeutic effect of DDP-based chemotherapy on advanced gastric carcinoma. Patients with XRCC1399 A/A genotype are more sensitive to DDP-based chemotherapy than those with other two genotypes.