Polymorphism of thymidylate synthase gene associated with its protein expression in human colon cancer.
OBJECTIVE
To correlate the polymorphisms in the 5'-untranslated region with thymidylate synthase (TS) protein expression in Han Chinese colonic neoplasms.


METHODS
Adenocarcinoma samples were from 68 patients who received no treatment before surgery. Tandem repeat length of TS gene was determined by PCR amplification of genomic DNA. Intratumoral TS protein expression was studied immunohistochemically in corresponding sections from paraffin-embedded primary foci. Immunoreactivity was semiquantitatively evaluated by immunoreactivity score (IRS).


RESULTS
Double-(2R) and triple-repeated (3R) sequences of the TS gene were found in the cancer tissues. Three genotypes of TS were found: 2R/2R (n=6), 2R/3R (n=22) and 3R/3R (n=40). Patients who were homozygous for triple-repeated (3R/3R) sequences showed significantly higher IRS of TS than patients who were homozygous for double-repeated (2R/2R) sequences or heterozygous patients (2R/3R): 5.73+/-3.25 vs 2.17+/-1.47 or 3.77+/-2.64, P=0.008 or P=0.015. But no statistical significance of IRS in cancer tissues was observed between 2R/3R genotype and 2R/2R genotype.


CONCLUSIONS
There is a relationship between TS genotype and TS protein expression in clinical specimens. The data might offer an advantage for selection of Chinese cancer patients to receive fluoropyrimidines treatment.
Yu
Kai-Huan
KH
Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Wang
Wei-Xing
WX
Ding
You-Ming
YM
Li
Hui
H
Wang
Ze-Sheng
ZS
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044466:Asian People / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism
D013940:Thymidylate Synthase