Polymorphisms of thymidylate synthase gene 5'- and 3'-untranslated region and risk of gastric cancer in Koreans.
BACKGROUND
Thymidylate synthase (TS) plays an important role in the conversion of dUMP to dTMP. Polymorphisms of the TS gene affect the expression of the gene, which in turn may result in differences in the outcome of cancer chemotherapy and the progression of gastric cancer.


METHODS
These types of TS polymorphism were investigated in 318 gastric cancer patients and 280 controls. A variable number of tandem repeats (VNTR; 2R or 3R) in the thymidylate synthase enhancer region (TSER), a G/C single nucleotide polymorphism within the second repeat sequence of 3R (3G or 3C), and a 6 bp insertion/deletion polymorphism (6 bp or 0 bp) in the TS 3'-untranslated region (3'-UTR) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Patients were sub-grouped by the Lauren classification.


RESULTS
The TSER 2R/2R genotype had a high odds ratio in gastric cancer and for the intestinal type, but was not statistically significant (adjusted odds ratio, AOR=2.31, 95% confidence interval, CI=0.94-5.65; and AOR=2.53, 95% CI=0.98-6.54, respectively). Among the combined genotypes of TSER VNTR-3'-UTR 6 bp ins/del, 2R2R-6 bp/6 bp having 4 risk alleles conferred a significantly high risk of gastric cancer, particularly of the intestinal type (AOR=8.70, 95% CI=1.09-68.93; and AOR=10.86, 95% CI=1.32-89.09, respectively).


CONCLUSIONS
Our results indicate that the 2R/2R-6 bp/6 bp combined genotype may be related to high gastric cancer susceptibility.
Yim
Dong Jin
DJ
Institute for Clinical Research, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam, 463-712, South Korea.
Kim
Ok Jun
OJ
An
Hee Jung
HJ
Kang
Haeyoun
H
Ahn
Dae Ho
DH
Hwang
Seong Gyu
SG
Oh
Doyeun
D
Kim
Nam Keun
NK
D020413:3' Untranslated Regions / Q000235:genetics*; D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D013940:Thymidylate Synthase