[Clinical significance of thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in Korean patients with gastric cancer].
OBJECTIVE
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.
Lee
Jun
J
Institute for Clinical Research, Department of Internal Medicine, Pochon CHA University College of Medicine, Bundang-gu, Seongnam, Korea.
Jeong
Cheol Kweon
CK
Hong
Sung Pyo
SP
Chong
So Young
SY
Oh
Doyeun
D
Hwang
Seong Gyu
SG
Ahn
Dae Ho
DH
Kim
Sehyun
S
Han
Jin Hee
JH
Kim
Nam Keun
NK
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase; D005472:Fluorouracil