Relationship of Polymorphism of the Tandem Repeat Sequence in the Thymidylate Synthase Gene and the Survival of Stage III Colorectal Cancer Patients Receiving Adjuvant 5-Flurouracil-Based Chemotherapy

초록

Background: 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. Methods: 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. Results: 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% Cl = 1.24-3.37, P = 0.005). Conclusions: TS polymorphisms do not predict clinical outcome of colorectal cancer patients treated with adjuvant 5-FU-based chemotherapy. J. Surg. Oncol. 2010;101:22-27. (C) 2009 Wiley-Liss, Inc.

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