title: Prognostic role of thymidylate synthase polymorphisms in gastric cancer patients treated with surgery and adjuvant chemotherapy.
abstract: OBJECTIVE
  To investigate the prognostic role of thymidylate synthase (TS) polymorphisms in gastric cancer patients treated with radical surgery and fluorouracil-based adjuvant chemotherapy.
  
  
  METHODS
  Ninety gastric cancer cases were identified among 187 patients previously enrolled in prospective case-control studies for disease susceptibility. Patients were genotyped for a G/C nucleotide change within a triple 28 bp variable number of tandem repeat sequence in the TS 5'-untranslated region (5'-UTR) and a 6 bp deletion in the TS 3'-untranslated region (3'-UTR). According to available functional data, patients with 5'-UTR 2R/2R, 2R/3C, 3C/3C genotypes were classified as low TS producers (5'-UTRlow) and patients with 5'-UTR 3G/3G, 3G/3C, 2R/3G genotypes as high TS producers (5'UTRhigh). Patients with 3'-UTR del6/del6 and del6/ins6 genotypes were classified as low TS producers (3'-UTRlow) and patients with 3'-UTR ins6/ins6 genotype as high TS producers (3'-UTRhigh). The prognostic analysis was based on 5'-UTR/3'-UTR combined genotypes.
  
  
  RESULTS
  Ten patients (11%) were 5'-UTRhigh/3'-UTRhigh, 36 patients were 5'-UTRhigh/3'-UTRlow, 19 patients were 5'-UTRlow/3'-UTRhigh, and 25 patients were 5'-UTRlow/3'-UTRlow. 5'-UTRlow/3'-UTRlow patients showed the best outcome and the threshold of statistical significance was achieved in the comparison of disease-free survival and overall survival with 5'-UTRhigh/3'-UTRlow patients and 5'-UTRhigh/3'-UTRhigh patients. The presence of at least one high TS expression genotype showed independent adverse prognostic role in multivariate analysis.
  
  
  CONCLUSIONS
  The prognostic role of TS polymorphisms in gastric cancer deserves further investigation because the adverse effect of high TS expression genotypes may be a relevant information to improve adjuvant chemotherapeutic strategies.
authors.affiliation: Department of Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kawakami
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Go
authors.initials: G
authors.lastname: Watanabe
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruzzo
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.forename: Renato
authors.initials: R
authors.lastname: Bisonni
authors.forename: Federica
authors.initials: F
authors.lastname: Arduini
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Pietro
authors.initials: P
authors.lastname: Muretto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrone
authors.forename: Carla
authors.initials: C
authors.lastname: Rabitti
authors.forename: Lucio
authors.initials: L
authors.lastname: Giustini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.forename: Francesca
authors.initials: F
authors.lastname: Pizzagalli
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D020080:Tandem Repeat Sequences; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D013940:Thymidylate Synthase