TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients.
OBJECTIVE
Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.


METHODS
251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5'-untranslated region of the TS gene were genotyped.


RESULTS
There was a positive association between tumor T stage and the VNTR genotypes (p=0.05).In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes.


CONCLUSIONS
We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.
Fariña-Sarasqueta
A
A
PAMM Laboratory for Pathology, Eindhoven, The Netherlands.
Gosens
M J E M
MJ
Moerland
E
E
van Lijnschoten
I
I
Lemmens
V E P P
VE
Slooter
G D
GD
Rutten
H J T
HJ
van den Brule
A J C
AJ
D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D020080:Tandem Repeat Sequences / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*
D000970:Antineoplastic Agents; D013940:Thymidylate Synthase; D005472:Fluorouracil