2019 年第 3 期 第 14 卷

胃癌患者氟尿嘧啶化疗疗效与P53基因多态性的相关性分析

Relation between fluorouracil chemotherapy efficacy and P53 gene polymorphism in gastric cancer patients

作者：朱贤章刘晖宋军兵李涛

英文作者：

单位：830001乌鲁木齐，新疆维吾尔自治区人民医院胃肠外科

英文单位：

关键词：胃肿瘤；P53基因；基因多态性；氟尿嘧啶

英文关键词：

• 摘要：

• 【摘要】目的    探讨P53基因多态性与胃癌患者氟尿嘧啶化疗疗效的关系。方法    选取2013年 3月至2015年3月新疆维吾尔自治区人民医院病理学确诊的胃癌患者110例，所有患者均接受含氟尿嘧啶的OFL方案化疗。采集患者外周静脉血提取基因组DNA，采用聚合酶链反应-连接酶检测反应（PCR-LDR）测序分型技术检测P53基因密码子72多态性，并分析其多态性与患者化疗疗效及无复发生存时间（RFS）和总生存时间（OS）的关系。结果    110例胃癌患者中，精氨酸/精氨酸基因型24例（21.8%），精氨酸/脯氨酸基因型59例（53.6%），脯氨酸/脯氨酸基因型27例（24.5%）。精氨酸/精氨酸基因型患者的化疗有效率明显高于精氨酸/脯氨酸和脯氨酸/脯氨酸基因型患者（均P＜0.05）。对110例化疗后的胃癌患者进行3年随访，结果发现，精氨酸/精氨酸基因型患者的RFS和OS最长，而脯氨酸/脯氨酸基因型患者的RFS和OS最短。COX多因素回归模型分析结果发现，P53基因多态性是影响氟尿嘧啶化疗胃癌患者RFS和OS的独立预后因素，其中脯氨酸/脯氨酸基因型是导致患者预后差的潜在危险因素（RFS：风险比=2.478,95%置信区间：1.752～5.730，P=0.028；OS：风险比=2.581,95%置信区间：1.052～6.330，P=0.038），TNM分期是氟尿嘧啶化疗胃癌患者OS短的危险因素（风险比=5.881,95%置信区间：2.123～17.221，P=0.002），但不影响患者的RFS（P＞0.05）。结论    P53基因密码子72多态性与胃癌患者对氟尿嘧啶化疗疗效和生存预后相关，具体表现为脯氨酸/脯氨酸基因型患者具有更低的化疗疗效和更短的RFS和OS。

• 【Abstract】Objective    To investigate the relation between P53 gene polymorphism and fluorouracil chemotherapy efficacy in gastric cancer patients. Methods    A total of 110 patients with gastric cancer who had fluorouracil OFL chemotherapy in People′s Hospital of Xinjiang Uygur Autonomous Region were enrolled from March 2013 to March 2015. Genomic DNA was extracted from peripheral venous blood. Polymorphism of P53 gene codon 72 was detected by polymerase chain reaction-ligase detection reaction. Relations of gene polymorphism with chemotherapy efficacy, recurrence free survival（RFS） and total survival（OS） were analyzed. Results    Among the 110 cases of gastric cancer, there were 24 cases(21.8%) of Arg/Arg genotype, 59 cases(53.6%)  of Arg/Pro genotype and 27 cases(24.5%) of Pro/Pro genotype. Effective rate of chemotherapy in patients with Arg/Arg genotype was significantly higher than that in patients with Arg/Pro genotype and Pro/Pro genotype(P＜0.05). During 3 years of follow-up, RFS and OS in Arg/Arg genotype patients were the longest; RFS and OS in Pro/Pro genotype patients were the shortest. COX multivariate regression model confirmed that P53 gene polymorphism is an independent predictive factor of RFS and OS in gastric cancer patients treated by fluorouracil chemotherapy; Pro/Pro genotype was a risk factor of poor prognosis（RFS： hazard ratio=2.478, 95% confidence interval： 1.752-5.730， P=0.028； OS： hazard ratio=2.581, 95% confidence interval： 1.052-6.330， P=0.038）. TNM staging was a risk factor of poor OS(hazard ratio=5.881, 95% confidence interval: 2.123-17.221, P=0.002) but has no influence on RFS (P<0.05). Conclusion    Polymorphism of P53 gene codon 72 is associated with fluorouracil chemotherapy efficacy and prognosis in gastric cancer patients; Pro/Pro genotype indicates poor efficacy and short survival time.