胸苷磷酸化酶多态性对结直肠癌患者接受卡培他滨的辅助化疗疗效的影响

摘要

Objective: To inrestigate the association between thymidine phosphorylase (TYMP) polymorphisms and efficacy of postop-erative capecitabine-based adjuvant chemotherapy in colorectal cancer (CRC) patients. Methods: Two hundred and thirty-five patients with colorectal cancer who received surgical treatment and adjuvant chemotherapy between January 2010 and December 2016 from People's Hospital of Zhengzhou, were included in this study. Peripheral blood and postoperative tissue specimens of the CRC patients were collected for genotyping polymorphisms and measuring TYMP mRNA expression, respectively. The correlation between the poly-morphisms and efficacy of postoperative chemotherapy in CRC patients was analyzed. Results: The prevalence of 5633C>T in TYMP gene among the CRC patients was as follows: CC genotype, 149 cases (63.40%); CT genotype, 73 cases (31.06%); and TT genotype, 13 cases (5.54%); the minor allele frequency of 5633C>T was 0.21. Survival analysis of the patients revealed that the median overall sur-vival (OS) of patients with the CT/TT genotype and those with the CC genotype was 5.9 and 4.5 years, respectively; the result was sta-tistically significant (P=0.009). Following adjustment in multivariate Cox regression analysis, the CT/TT genotype was found to be an in-dependent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, results show that the levels of TYMP mRNA in cancer tissues of patients with the CT/TT genotype were significantly higher than those with the CC genotype (P=0.019). Conclusions: TYMP mRNA expression may be influenced by the 5633C>T polymorphism, making CRC patients benefit from capecitabine treatment.%目的:本研究旨在探讨胸苷磷酸化酶(thymidine phosphorylase,TYMP)基因多态性对R0术后结直肠癌(colorectal cancer, CRC)患者接受卡培他滨为基础的辅助化疗疗效的影响.方法:本研究纳入2010年1月至2016年12月在郑州人民医院行R0切除术后接受辅助化疗的CRC患者235例.收集患者外周血及术后癌组织标本分别进行TYMP多态性位点基因分型及TYMP基因表达测定,并对纳入研究患者的疗效进行关联性分析.结果:TYMP基因5633C>T位点在CRC患者中的分布频率为:CC型149例(63.40%),CT型73例(31.06%),TT型13例(5.54%),最小等位基因频率为0.21.单变量的生存分析结果显示:携带T等位基因的CT/TT型患者和野生型CC型患者的中位总生存期(overall survival,OS)分别为5.9和4.5年,差异具有统计学意义(P=0.009).经过多变量的Cox模型校正之后发现CT/TT基因型患者对OS有独立的影响(HR=0.67,P=0.015).另外,进一步在87例癌组织标本的mRNA表达分析中发现,突变的CT/TT型患者癌组织中TYMP的mRNA表达显著高于CC型患者(P=0.019).结论:TYMP基因5633C>T位点可能通过影响该基因mRNA的表达进而使CRC患者从卡培他滨的治疗中获益.