Expression of genes for 5-FU-metabolizing enzymes and response to irinotecan plus 5-FU-leucovorin in colorectal cancer

Abstract

Background: 5-Fluorouracil (5-FU) is initially catabolized by dihydropyrimidine dehydrogenase. Thymidylate synthase (TS) is the target enzyme of 5-FU. In addition, activation of 5-FU to form various nucleotides via three pathways requires phosphorylation by orotate phosphoribosyltransferase, thymidine phosphorylase and uridine phosphorylase, respectively. The aim of this study was to assess the predictive value of the expression of these genes in patients receiving irinotecan plus 5-FU/leucovorin therapy (IFL) for colorectal cancer.

Patients and methods: Twenty-seven patients with metastatic, or recurrent colorectal cancer were studied. Enzyme gene expression was measured in primary tumors by the real-time reverse transcription PCR method.

Results: The TS mRNA level was significantly higher in the responders than in the non-responders (p=0.0409).

Conclusion: The effect of IFL therapy may be determined by the extent of TS mRNA expression. It is suggested that assay of TS mRNA may be useful for predicting the effect of intravenous regimens such as FOLFIRI.