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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
Author(s) -
Park ChiMin,
Lee Woo Yong,
Chun HoKyung,
Cho Yong Beom,
Yun Hae Ran,
Heo Jin Seok,
Yun Seong Hyeon,
Kim Hee Cheol
Publication year - 2009
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21412
Subject(s) - thymidylate synthase , colorectal cancer , medicine , genotype , single nucleotide polymorphism , oncology , tandem repeat , stage (stratigraphy) , hazard ratio , chemotherapy , variable number tandem repeat , snp , fluorouracil , gastroenterology , cancer , gene , biology , genetics , confidence interval , paleontology , genome
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% CI = 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. © 2009 Wiley‐Liss, Inc.