PURPOSE: To investigate the prognostic role of thymidylate synthase (TS) polymorphisms in gastric cancer patients treated with radical surgery and fluorouracil-based adjuvant chemotherapy. 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. 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.
PURPOSE: To investigate the prognostic role of thymidylate synthase (TS) polymorphisms in gastric cancerpatients treated with radical surgery and fluorouracil-based adjuvant chemotherapy. 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. 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: G Visani; F Loscocco; A Ruzzo; S Galimberti; F Graziano; M T Voso; E Giacomini; C Finelli; E Ciabatti; E Fabiani; S Barulli; A Volpe; D Magro; P Piccaluga; F Fuligni; M Vignetti; P Fazi; A Piciocchi; E Gabucci; M Rocchi; M Magnani; A Isidori Journal: Pharmacogenomics J Date: 2017-12-05 Impact factor: 3.550
Authors: Elizabeth Smyth; Shenli Zhang; David Cunningham; Andrew Wotherspoon; Richie Soong; Clare Peckitt; Nicola Valeri; Matteo Fassan; Massimo Rugge; Alicia Okines; William Allum; Sally Stenning; Matthew Nankivell; Ruth Langley; Patrick Tan Journal: Clin Cancer Res Date: 2017-10-02 Impact factor: 12.531