胃癌患者叶酸代谢通路相关基因的多态性与卡培他滨联合紫杉醇化疗后生存期的关系

Relationship between polymorphisms of related genes in the folic acid metabolic pathway and the survival of gastric cancer patients treated with capecitabine combined with paclitaxel

目的:研究胃癌患者的叶酸代谢通路相关基因和肿瘤相关候选基因的多态性与卡培他滨联合紫杉醇化疗后生存期的关系。方法:选取经病理学确诊的胃癌患者93例,采用卡培他滨联合紫杉醇为主的方案进行化疗。以TaqMan-MGB探针方法进行基因分型,包括肿瘤坏死因子(tumor necrosis factor,TNF)A308G(rs1800629)、亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)C677T(rs1801131)及A1298C(rs1801133)、甲硫氨酸合成酶(methionine synthase,MS或MTR)A2756G(rs1805087)和甲硫氨酸合成还原酶(methionine synthase reductase,MTRR)A66G(rs1801394)基因的分型。比较不同基因型患者在化疗后的中位生存时间(median survival time,MST),以及各种因素对其预后的影响。结果:中位随访时间为29.6个月,93例患者的MST为34.93个月。MTHFR A1298C中携带CA基因型胃癌患者的MST为47.50个月,CC基因型患者的MST为22.91个月;经log-rank检验发现,MTHFR1298C/A基因多态性与患者生存期有边际显著性关系(χ2=3.447,P=0.062)。其他基因型多态性与胃癌患者的生存期无显著相关性。COX回归分析显示,性别、酗酒和手术是胃癌患者化疗后预后的主要影响因素。结论:检测MTHFR1298C/A位点基因多态性可在一定程度上预测卡培他滨联合紫杉醇化疗后胃癌患者的生存情况。

Objective：To investigate the association of polymorphisms of related genes in folic acid metabolic pathway and the tumor candidate genes with the survival of gastric cancer patients treated with capecitabine combined with paclitaxel.Methods：Ninety-three patients with pathological diagnosis of gastric cancer were treated with capecitabine plus paclitaxel-based chemotherapy.The gene polymorphisms of tumor necrosis factor（TNF） A308G（rs1800629）,methylenetetrahydrofolate reductase（MTHFR） C677T（rs1801131） and A1298C（rs1801133）,methionine synthase（MTR） A2756G（rs1805087） and methionine synthase reductase（MTRR） A66G（rs1801394） were detected by TaqMan-MGB probe typing method.The median survival time（MST） of patients with different genotypes was compared,and the effects of various factors on the prognosis were evaluated.Results：The median follow-up period was 29.6 months.The MST of 93 patients was 34.93 months.The MST of patients with MTHFR 1298CA and 1298CC were 47.50 and 22.91 months,respectively.The log-rank test revealed that the polymorphism of MTHFR 1298C/A had marginally significant correlation with the survival of patients（χ2=3.447,P=0.062）,and other gene polymorphisms were not associated with the survivals.The gender,drinking and operation were the major prognostic factors for gastric cancer patients receiving chemotherapy.Conclusion：Detection of MTHFR 1298CA polymorphism may predict the survival of gastric cancer patients receiving chemotherapy of capecitabine combined with paclitaxel.