Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea.
J Surg Oncol. 2010 Jan 1;101(1):22-7. doi: 10.1002/jso.21412.
The aim of this study was to determine whether the different polymorphisms in the thymidylate synthase (TS) gene, novel G>C single nucleotide polymorphism (SNP) and variable number of tandem repeat (VNTR), may be related with disease-free survival (DFS) in patients with stage III colorectal cancer receiving adjuvant chemotherapy.
The study included 201 patients with pathologic TNM stage III colon cancer who received adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgery. DNA was extracted from fresh tumor tissue and sequenced. Patients with TS genotypes of 2R3G, 3C3G, or 3G3G were assigned to a high expression group, and those with 2R2R, 2R3C, or 3C3C, to a low expression group.
Frequencies of the TS tandem repeat polymorphisms among the tumor genotypes were 6.0% in 2R2R, 25.4% in 2R3R, and 68.7% in 3R3R. The low expression group included 52 patients (25.9%), and the high expression group included 149 patients (74.1%). Groups classified according to possession of VNTR, SNP, and low- or high-expression genotypes did not differ significantly in DFS. In multivariate analysis, only tumor stage showed significant prognostic value (hazard ratio (HR) 2.05, 95% CI = 1.24-3.37, P = 0.005).
TS polymorphisms do not predict clinical outcome of colorectal cancer patients treated with adjuvant 5-FU-based chemotherapy.
本研究旨在确定胸苷酸合成酶（TS）基因的不同多态性，即新的 G>C 单核苷酸多态性（SNP）和可变串联重复（VNTR），是否与接受辅助化疗的 III 期结直肠癌患者的无病生存（DFS）相关。
本研究纳入了 201 例病理 TNM 分期为 III 期结肠癌患者，这些患者在手术后接受了 5-氟尿嘧啶（5-FU）为基础的辅助化疗。从新鲜肿瘤组织中提取 DNA 并进行测序。将 TS 基因型为 2R3G、3C3G 或 3G3G 的患者分配到高表达组，将 TS 基因型为 2R2R、2R3C 或 3C3C 的患者分配到低表达组。
肿瘤基因型中 TS 串联重复多态性的频率分别为 2R2R 为 6.0%、2R3R 为 25.4%和 3R3R 为 68.7%。低表达组包括 52 例患者（25.9%），高表达组包括 149 例患者（74.1%）。根据 VNTR、SNP 以及低表达或高表达基因型进行分组的两组患者在 DFS 方面无显著差异。多变量分析显示，仅肿瘤分期具有显著的预后价值（风险比（HR）2.05，95%置信区间（CI）为 1.24-3.37，P=0.005）。
TS 多态性不能预测接受辅助 5-FU 化疗的结直肠癌患者的临床结局。
