Thymidylate synthase gene polymorphism as a prognostic factor for colon cancer.

The human thymidylate synthase (TS) gene promoter is polymorphic, having either double or triple tandem repeats of a 28-base-pair (bp) sequence. Here, we determined the significance of this polymorphism in predicting the clinical outcomes for patients with colon cancer. We reviewed 121 consecutive patients with stage II or III colon cancer who underwent a curative resection. After DNA extraction from paraffin-embedded tissues, the promoter region of the TS gene was amplified by polymerase chain reaction. In addition to the conventional prognostic factors, patient survivals were compared with regard to the pattern of TS polymorphism. Sixty-eight subjects were homozygotes for the triple-repeat variant (250 bp, group A), and 53 subjects (group B) were either homozygotes for the double-repeat variant (220 bp) or heterozygotes (220 and 250 bp). We found a significant difference between groups A and B in survival (53% versus 80%, P=0.0481). The difference was particularly significant in the patients with stage III disease (41% versus 77%, P=0.0414). Tumor stage and the TS polymorphism were identified as significant prognostic factors by multivariate analysis. We found the TS polymorphism to be a significant and independent prognostic factor for colon cancer.