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

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 PI-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 GSTPI-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 GSTPI polymorphisms may allow identification of gastric cancer patients who will benefit from 5-FU/cisplatin chemotherapy, sparing others the side effects of this chemotherapy.