Molecular Diagnostics

British Journal of Cancer (2006) 94, 281–286. doi:10.1038/sj.bjc.6602891 www.bjcancer.com
Published online 29 November 2005

Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS) – novel predictors for response and survival in gastric cancer patients

E Goekkurt1,2, S Hoehn1, C Wolschke1, C Wittmer3, C Stueber1, D K Hossfeld1 and J Stoehlmacher1,2

  1. 1Department of Haematology and Oncology, University Hospital Hamburg Eppendorf, University of Hamburg, Germany
  2. 2Department of Internal Medicine I, University Hospital Carl Gustav Carus, University Dresden, Germany
  3. 3Department of Pathology, University Hospital Hamburg Eppendorf, University of Hamburg, Germany

Correspondence: Dr J Stoehlmacher, E-mail: jan.stoehlmacher@uniklinikum-dresden.de

Received 8 August 2005; Revised 12 October 2005; Accepted 27 October 2005; Published online 29 November 2005.

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Abstract

To evaluate the predictive value of a panel of gene polymorphisms involved in metabolism of 5-FU and cisplatin on clinical outcome in advanced gastric cancer patients. A total of 52 patients were enrolled in this study. DNA was extracted from paraffin-embedded tumour specimen. Genotypes were determined using PCR-RFLP. Median survival time was 6.0 months (95% CI 3.9;8.1). Overall response rate was 26%. Patients possessing the glutathione S-transferase P1-105 Valine/Valine (GSTP1-105VV) genotype showed a response rate of 67% compared to 21% in patients harbouring at least one GSTP1-105 Isoleucine (GSTP1-105I) allele (P=0.038). GSTP1-105VV patients demonstrated a significant superior median survival time of 15.0 months (95% CI 7.8;22.0) compared to 6.0 months (95% CI 5.1;7.0) in patients with at least one GSTP1-105I allele (P=0.037). Patients possessing a favourable thymidylate synthase (TS) genotype (2R/2R, 2R/3RC, 3RC/3RC) experienced a superior survival time of 10.2 months (95% CI 5.1;15.3) compared to 6.0 months (95% CI 5.0;7.0) in patients with unfavourable TS genotypes (P=0.099). Patients harbouring the GSTP1-105II genotype and one of the unfavourable TS genotypes showed an inferior median survival time of 6.0 months (95% CI 3.9;8.1) compared to 11 months (95% CI 6,23;15,77) in patients with either GSTP1-105VV or a favourable TS genotype (P=0.044). Testing for TS and GSTP1 polymorphisms may allow identification of gastric cancer patients who will benefit from 5-FU/cisplatin chemotherapy, sparing others the side effects of this chemotherapy.

Keywords:

glutathione S-transferase P1, thymidylate synthase, pharmacogenetics, gastric cancer, 5-FU/cisplatin