| 张胜威,邓业巍,李晓洁.胸苷磷酸化酶rs11479位点多态性对术后结直肠癌患者接受卡培他滨为基础辅助化疗疗效的影响[J].肿瘤学杂志,2019,25(4):305-309. |
| 胸苷磷酸化酶rs11479位点多态性对术后结直肠癌患者接受卡培他滨为基础辅助化疗疗效的影响 |
| Association between Thymidine Phosphorylase Polymorphism and Clinical Outcomes of Postoperative Colorectal Cancer Patients with Capecitabine Based Adjuvant Chemotherapy |
| 投稿时间：2018-03-01 |
| DOI：10.11735/j.issn.1671-170X.2019.04.B004 |
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| 中文关键词: 结直肠肿瘤 胸苷磷酸化酶 卡培他滨 多态性 |
| 英文关键词:colorectal cancer thymidine phosphorylase capecitabine polymorphism |
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| 中文摘要: |
| 摘 要：［目的］ 探讨胸苷磷酸化酶（Thymidine Phosphorylase，TYMP）的基因变异对术后结直肠癌(colorectal cancer，CRC)患者接受辅助化疗疗效的影响。［方法］ 纳入198例术后接受辅助化疗的结直肠癌患者，收集患者外周血及术后癌组织标本进行TYMP基因rs11479分型及TYMP基因表达测定。Rs11479位点的基因型和其他变量的相关性通过logistic回归模型进行分析。不同基因型的TYMP mRNA表达通过非参数检验分析，基因型和预后的单变量分析用Kaplan-Meier生存分析方法，并通过Cox风险比例模型对其他变量进行校正。［结果］ TYMP基因rs11479位点在CRC患者中的突变频率为：CC型126例（63.64%），CT型61例（30.81%），TT型11例（5.55%），最小等位基因频率为0.21，三种基因型分布频率符合哈迪温伯格平衡（P=0.323）。在预后比较上，将CT型和TT型患者合并，单变量的生存分析结果显示：野生型的CC型患者无复发生存（DFS）显著低于携带突变基因的CT型和TT型患者（P=0.002）。经多变量Cox模型校正之后发现CC基因型患者的预后影响意义依然存在（P=0.012）。87例癌组织标本的mRNA表达分析中发现，突变的CT或TT型患者相对于野生型的CC型患者，癌组织中TYMP的mRNA表达明显较高（P=0.019）。［结论］ 在结直肠癌患者中，TYMP基因rs11479位点可能通过影响TYMP基因mRNA的表达从而使更多的卡培他滨代谢为5-Fu进而使CRC患者从卡培他滨的治疗中获益。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the association between Thymidine Phosphorylase(TYMP) polymorphism and clinical outcomes of postoperative colorectal cancer(CRC) patients treated with capecitabine based adjuvant chemotherapy. ［Methods］ One hundred and ninety-eight patients with colorectal cancer，who underwent surgical treatment and received postoperative capecitabine based adjuvant chemotherapy，were enrolled in the study. Peripheral blood and cancer tissue specimen were collected for TYMP rs11479 genotyping and TYMP mRNA expression detecting，respectively. The correlation of rs11479 genotypes and other variables was analyzed by logistic regression model. The expression of TYMP in different genotypes was analyzed by non-parametric test. The survival of patients was analyzed with Kaplan-Meier method，the association between TYMP genotypes and survival of patients was examined with univariate and multivariate Cox regression analysis. ［Results］ The prevalence of TYMP rs11479 genotype CC was 63.64%(126/198)，genotype CT was 30.81%(61/198)，genotype TT was 5.55%(11/198). The minor allele frequency of rs11479 was 0.21，the distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium(P=0.323). There were no statistical differences in the distribution of the genotypes in baseline clinical data. The disease-free survival(DFS) of patients with wild genotype CC was significantly lower than that of those with CT and TT genotypes(P=0.002). Multivariate Cox regression analysis showed that CC genotype was an independent factor for poor DFS(P=0.012). The expression of TYMP mRNA in cancer tissues of the patients with CT or TT genotypes was significantly higher than that of CC genotype patients(P=0.019). ［Conclusion］ TYMP gene expression may be affected by the rs11479 polymorphism，which might be associated with the efficacy of capecitabine based adjuvant chemotherapy in postoperative CRC patients. |
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