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Kawakami, Kazuyuki; Graziano, Francesco; Watanabe, Go; Ruzzo, Annamaria; Santini, Daniele; Catalano, Vincenzo; Bisonni, Renato; Arduini, Federica; Bearzi, Italo; Cascinu, Stefano; Muretto, Pietro; Perrone, Giuseppe; Rabitti, Carla; Giustini, Lucio; Tonini, Giuseppe; Pizzagalli, Francesca; Magnani, Mauro

Prognostic Role of Thymidylate Synthase Polymorphisms in Gastric Cancer Patients Treated with Surgery and Adjuvant Chemotherapy

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  • Medientyp: E-Artikel
  • Titel: Prognostic Role of Thymidylate Synthase Polymorphisms in Gastric Cancer Patients Treated with Surgery and Adjuvant Chemotherapy
  • Beteiligte: Kawakami, Kazuyuki; Graziano, Francesco; Watanabe, Go; Ruzzo, Annamaria; Santini, Daniele; Catalano, Vincenzo; Bisonni, Renato; Arduini, Federica; Bearzi, Italo; Cascinu, Stefano; Muretto, Pietro; Perrone, Giuseppe; Rabitti, Carla; Giustini, Lucio; Tonini, Giuseppe; Pizzagalli, Francesca; Magnani, Mauro
  • Erschienen: American Association for Cancer Research (AACR), 2005
  • Erschienen in: Clinical Cancer Research
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-04-2428
  • ISSN: 1078-0432; 1557-3265
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>Purpose: To investigate the prognostic role of thymidylate synthase (TS) polymorphisms in gastric cancer patients treated with radical surgery and fluorouracil-based adjuvant chemotherapy.</jats:p> <jats:p>Experimental Design: 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.</jats:p> <jats:p>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.</jats:p> <jats:p>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.</jats:p>
  • Zugangsstatus: Freier Zugang