title: Polymorphic thymidylate synthase gene impacts on overall survival of patients with epithelial ovarian cancer after platinum-based chemotherapy.
abstract: OBJECTIVE
  High levels of TS have been associated with a worse clinical outcome in several cancers including epithelial ovarian cancer (EOC). The TS gene (TYMS) is highly polymorphic and has an effect on mRNA/protein expression.
  
  
  METHODS
  Six TYMS polymorphisms were investigated for overall survival (OS) in 216 EOC patients: TYMS 1494ins/del, TSER (variable number of tandem repeats of 28 bp), TSER G>C, TYMS 1053C>T, TYMS IVS6-68C>T and TYMS 1122A>G.
  
  
  RESULTS
  In a multivariate analysis, TYMS 1494 del/del genotype was associated with a significant increased OS compared with the ins/ins genotype (hazard ratio: 0.36; 95% CI: 0.16-0.82, p = 0.01). Similar results were obtained for the mutant genotypes TYMS 1053TT and TYMS IVS6-68TT. The event-free survival was significantly higher in TYMS 1053TT patients compared with wild-type patients (p = 0.05).
  
  
  CONCLUSIONS
  TYMS 1494ins/del, 1053C>T and IVS6-68C>T polymorphisms can be prognostic markers for OS in patients with EOC, independently from stage at diagnosis, median age and tumor histotype.
authors.affiliation: Experimental & Clinical Pharmacology Unit, Centro di Riferimento Oncologico - National Cancer Institute, Via Franco Gallini 2, 33081 Aviano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Biason
authors.forename: Michele
authors.initials: M
authors.lastname: Visentin
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Alex
authors.initials: A
authors.lastname: Stopar
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giorda
authors.forename: Emilio
authors.initials: E
authors.lastname: Lucia
authors.forename: Elio
authors.initials: E
authors.lastname: Campagnutta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D054316:Biomarkers, Pharmacological; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010984:Platinum / Q000008:administration & dosage*; D011379:Prognosis; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D054316:Biomarkers, Pharmacological; D010984:Platinum; D013940:Thymidylate Synthase