Polymorphism of thymidylate synthase gene and chemosensitivity of 5-fluorouracil regimen in metastatic gastrointestinal cancer

Abstract

Objective: To explore the polymorphism of thymidylate synthase (TS) gene and chemosensitivity of a 5-fluorouracil (5-FU)-containing regimen in metastatic colorectal and gastric cancer. Methods: Sixty-eight patientswith metastatic gastric or colorectal cancer were included in this study. Doublets or triplets of 28 base pairs (bp) in the 5-untranslated region (UTR) of TS gene promoter were detected by polymerase chain reaction (PCR) analysis. Fragments of polymorphic products, 2R/2R, 2R/3R and 3R/3R were detected by the Agilent BioAnalyzer chip-lab system. All patients were followed up until the censoring date. A χ test was used to analyze the polymorphism. A Kaplan-Meier curve and a log-rank test were used to determine disease progression and overall survival. Results: Among 68 patients, polymorphism expressions were 4.4% in 2R/2R, 29.4% in 2R/3R and 66.2% in 3R/3R, and clinical responses were 33.3%, 73.3% and 47.6%, respectively (2R/3R versus 3R/3R, P = 0.058). In the 64 evaluable cases, the median time to progression (TTP) was 4 months and the TTP were 3 months in 2R/2R, 6 months in 2R/3R and 4 months in 3R/3R, separately (log-rank test, P = 0.0316). Response rates to the 5-FU regimen were also better in the 2R/3R group than in the 3R/3R group both in metastatic colorectal cancer and advanced gastric cancer. Conclusion: Our study suggested that polymorphism of 3R/3R was more common in Chinese gastrointestinal cancer patients. Patients with a TS polymorphism expressed as 2R/3R might be more sensitive to 5-FU regimen than those with a polymorphism expressed as 3R/3R. © Journal compilation © 2009 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology and Blackwell Publishing Asia Pty Ltd.