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| Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS) - novel predictors for response and survival in gastric cancer patients |
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| Author(s): Goekkurt E, Hoehn S, Wolschke C, Wittmer C, Stueber C, Hossfeld DK, Stoehlmacher J |
| Source: BRITISH JOURNAL OF CANCER Volume: 94 Issue: 2 Pages: 281-286 Published: JAN 30 2006 |
| Times Cited: 46 References: 45 |
| 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 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Stoehlmacher, J (reprint author), Univ Hamburg, Hosp Eppendorf, Dept Haematol & Oncol, Martinistr 52, D-20246 Hamburg, Germany |
Addresses:
1. Univ Hamburg, Hosp Eppendorf, Dept Haematol & Oncol, D-20246 Hamburg, Germany
2. Univ Dresden, Dept Internal Med 1, Univ Hosp Carl Gustav Carus, Dresden, Germany
3. Univ Hamburg, Hosp Eppendorf, Dept Pathol, Hamburg, Germany |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Oncology |
| IDS Number: 010JF |
| ISSN: 0007-0920 |
| DOI: 10.1038/sj.bjc.6602891 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |