Polymorphism of thymidylate synthase gene and chemosensitivity of 5-fluorouracil regimen in metastatic gastrointestinal cancer.
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 patients with 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 chi2 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.


CONCLUSIONS
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.
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Yue Hong
YH
Cui
Tian Shu
TS
Liu
Rong Yuan
RY
Zhuang
Hen Jun
HJ
Gao
Hong
H
Li
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D013940:Thymidylate Synthase / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil