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.

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.