[Polymorphisms of thymidylate synthase gene and correlation of its protein expression to lymph node metastasis of esophageal squamous cell carcinoma].
OBJECTIVE
Thymidylate synthase (TS) is a key enzyme in DNA synthesis. The 28-bp tandem repeat in the 5'-untranslated region (UTR) of TS gene and the G/C single nucleotide polymorphism (SNP) of TS gene may modify the expression and activity of TS protein, therefore, may change the susceptibility and prognosis of tumors. This study was to explore the correlations of TS 5'-UTR polymorphism to lymph node metastasis of esophageal squamous cell carcinoma (ESCC) and the expression of TS protein.


METHODS
Peripheral leucocyte DNA was extracted from 232 ESCC patients and 348 age-and gender-matched healthy controls. TS 5'-UTR tandem repeat and the G/C SNP genotype was detected by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. TS expression in 51 specimens of ESCC was detected by SP immunohistochemistry.


RESULTS
The frequencies of 3G/3G, 3G/3C, 3C/3C, 2R/3G, 2R/3C, 2R/2R, and other genotypes were 17.5%, 17.3%, 29.3%, 12.9%, 17.8%, 3.7%, and 1.5% in the healthy controls, and 16.0%, 16.0%, 29.3%, 13.8%, 17.6%, 4.3%, and 3.0% in the ESCC patients; whereas the frequencies of 3G, 3C, 2R, and other alleles were 32.8%, 47.0%, 19.5%, and 0.7% in the healthy controls, and 31.2%, 46.8%, 20.5%, and 1.5% in the ESCC patients, respectively. Compared with 3G/3G genotype, 2R/3G genotype significantly increased the risk of lymph node metastasis of ESCC [age and gender adjusted odds ratio (OR), 11.53; 95% confidence interval (CI), 2.67-49.74]. TS protein expression was significantly related to TS 5'-UTR genotype (P<0.05), but was not related to gender, age, lymph node metastasis and clinicopathologic stage.


CONCLUSIONS
TS 5'-UTR tandem repeat and G/C SNP genotype, but not TS expression, might be a candidate molecular marker to predict lymph node metastasis of ESCC.
Dong
Zhi-Ming
ZM
Pathology Laboratory, Hebei Provincial Cancer Institute, Shijiazhuang, Hebei, P. R. China.
Cui
Ya-Jing
YJ
Kuang
Gang
G
Wang
Rui
R
Yu
Feng-Ling
FL
Zhang
Jian-Hui
JH
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020080:Tandem Repeat Sequences; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase