Polymorphic thymidylate synthase gene impacts on overall survival of patients with epithelial ovarian cancer after platinum-based chemotherapy

Paola Biason, Michele Visentin, Renato Talamini, Alex Stopar, Giorgio Giorda, Emilio Lucia, Elio Campagnutta, Giuseppe Toffoli

Research output: Contribution to journalArticle

Abstract

Aim: 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. Materials & 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). Conclusion: 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. Original submitted 11 May 2012; Revision submitted 10 August 201.

Original languageEnglish
Pages (from-to)1609-1619
Number of pages11
JournalPharmacogenomics
Volume13
Issue number14
DOIs
Publication statusPublished - Nov 2012

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Keywords

  • EOC
  • epithelial ovarian cancer
  • OS
  • overall survival
  • platinum
  • polymorphism
  • thymidylate synthase
  • TYMS

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine

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