Thymidylate synthase germline polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy based on 5-fluorouracil

David Páez, Laia Paré, Albert Altés, Francesc Josep Sancho-Poch, Lourdes Petriz, Jordi Garriga, Josep Maria Monill, Juliana Salazar, Elisabeth Del Rio, Agustí Barnadas, Eugenio Marcuello, Montserrat Baiget

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23 Citations (Scopus)

Abstract

Purpose: Chemoradiotherapy using 5-fluorouracil has shown to be effective treatment for rectal cancer. Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. However, the predictive role of TS levels in early stage rectal cancer is not yet well understood. We analyzed the value of TS gene polymorphisms as a predictive marker in patients with stage II and III rectal cancer treated with preoperative concomitant radiotherapy and fluoropyrimidine-based chemotherapy. Methods and materials: Between 1998 and 2007, blood samples were obtained from 51 patients with stage II/III rectal cancer. Forty patients were T2-3 (78%), 11 were T4 (22%), and 59% were N+. DNA was extracted from peripheral blood, and the genotypes were analyzed using PCR-restriction fragment length polymorphism and automated sequencing techniques. Results: The 3/ 3 thymidylate synthase genotype was associated with a higher response rate (pathological complete remission and microfoci residual tumor; 61 vs. 22% in 2/ 2 and 2/ 3; P = 0.013). In the multivariate analysis, the 3/ 3 thymidylate synthase genotype was also an independent prognostic factor for better survival (P < 0.05). Conclusions: The thymidylate synthase genotype might help to identify patients with stage II/III rectal cancer who could benefit from pre- and postoperative fluorouracil-based chemotherapy. © 2010 Springer-Verlag.
Original languageEnglish
Pages (from-to)1681-1689
JournalJournal of Cancer Research and Clinical Oncology
Volume136
Issue number11
DOIs
Publication statusPublished - 1 Nov 2010

Keywords

  • 5-Fluorouracil
  • Chemoradiation
  • Pharmacogenetics
  • Rectal Cancer
  • TS polymorphism

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