title: TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients.
abstract: 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.
authors.affiliation: PAMM Laboratory for Pathology, Eindhoven, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Fariña-Sarasqueta
authors.forename: M J E M
authors.initials: MJ
authors.lastname: Gosens
authors.forename: E
authors.initials: E
authors.lastname: Moerland
authors.forename: I
authors.initials: I
authors.lastname: van Lijnschoten
authors.forename: V E P P
authors.initials: VE
authors.lastname: Lemmens
authors.forename: G D
authors.initials: GD
authors.lastname: Slooter
authors.forename: H J T
authors.initials: HJ
authors.lastname: Rutten
authors.forename: Adriaan J C
authors.initials: AJ
authors.lastname: van den Brule
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D017677:Age Distribution; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D020121:5' Untranslated Regions; D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D005472:Fluorouracil