GI Division, Shanghai Institution of Digestive Disease, School of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, 200001, China.
Mol Biol Rep. 2013 Jul;40(7):4637-44. doi: 10.1007/s11033-013-2557-8. Epub 2013 May 5.
Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC). This meta-analysis aimed to elucidate the effect of Ts polymorphisms on the efficacy of 5-FU-based chemotherapy in GC and CRC patients. Individual data were analyzed from 10 studies of 1102 GC and CRC patients treated with 5-FU-based regimens. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Data were pooled using the program STATA version 10.0 (Stata Corporation, College Station, TX). The relationship between the Ts polymorphism and survival following 5FU-based treatment of GC and CRC patients was systematically summarized. Compared with the C allele, the G allele was associated with shorter PFS but with similar OS in Caucasian CRC patients. Compared with the 3R/3R genotype, the 2R/3R or 2R/2R genotype was associated with the same PFS, but with a shorter OS, particularly in Caucasian CRC patients. These results show a correlation between survival following 5-FU-based therapy and tumor genotype in Caucasian CRC patients. Larger studies and further clinical trials are required to confirm this observation.
胸苷酸合成酶是 5-氟尿嘧啶（5-FU）的主要靶点，5-FU 被广泛用于治疗胃癌（GC）和结直肠癌（CRC）。本荟萃分析旨在阐明 Ts 多态性对 GC 和 CRC 患者接受 5-FU 为基础的化疗疗效的影响。从接受 5-FU 为基础方案治疗的 10 项研究中，对 1102 例 GC 和 CRC 患者的个体数据进行了分析。主要观察终点为总生存（OS）和无进展生存（PFS）。使用 STATA 版本 10.0（Stata Corporation，College Station，TX）程序进行数据汇总。系统总结了 Ts 多态性与 GC 和 CRC 患者接受 5-FU 治疗后的生存之间的关系。与 C 等位基因相比，G 等位基因与 CRC 患者的较短 PFS 相关，但与相似的 OS 相关。与 3R/3R 基因型相比，2R/3R 或 2R/2R 基因型与相同的 PFS 相关，但 OS 更短，特别是在 CRC 患者中。这些结果表明，5-FU 为基础的治疗后生存与白种人 CRC 患者的肿瘤基因型之间存在相关性。需要更大规模的研究和进一步的临床试验来证实这一观察结果。
