Clinical Significance of Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Korean Patients with Gastric Cancer / 대한소화기학회지

ABSTRACT

BACKGROUND/AIMS: Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU) and has a polymorphic 28 bp tandem repeated sequence. TS enhancer region (TSER) polymorphism has been associated with the efficacy of 5-FU-based chemotherapy in colon cancer. Methylenetetrahydrofolate reductase (MTHFR) plays a central role in converting folate to methyl donor for DNA methylation. The aim of this study was to determine the clinical value of TSER and MTHFR polymorphism in gastric cancer. METHODS: From October, 1995 to February, 2002, 40 gastric cancer patients underwent operation and 25 patients among those patients have received postoperative 5-FU-based chemotherapy (5-FU (+) group). Peripherial blood were sampled for TSER and MTHFR genotype analysis by PCR amplification of genomic DNA. The survival of patients according to TSER and MTHFR polymorphism were compared. RESULTS: We observed a longer survival in stage II than stage III of the patients (p=0.0037). However, the TSER and MTHFR C677T polymorphisms were not associated with better survival of gastric cancer patients as well as combined TSER and MTHFR genotypes with 5-FU chemotherapy. CONCLUSIONS: The TSER and MTHFR genotypes are not effective markers for tumor sensitivity to 5-FU-based chemotherapy in Korean gastric cancer patients after curative resection. These results may suggest further large-scale study about TSER and MTHFR polymorphism for the prediction of efficacy of 5-FU-based chemotherapy in gastric cancer in Korea.