Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer
| Autor: | Dirk Sleijfer, Coby Meijer, Jourik A. Gietema, Nynke Zwart, Gerrit van der Steege, H. Marike Boezen, Janine Nuver, Esther C. de Haas, Albert J. H. Suurmeijer, Harald J. Hoekstra |
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| Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG, Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cancer Research Adolescent Genotype Pulmonary Fibrosis COMBINATION CHEMOTHERAPY EUROPEAN-ORGANIZATION Single-nucleotide polymorphism Bleomycin Polymorphism Single Nucleotide Cohort Studies chemistry.chemical_compound CISPLATIN Testicular Neoplasms Antineoplastic Combined Chemotherapy Protocols medicine Humans CRYSTAL-STRUCTURE Survival rate Etoposide Polymorphism Genetic business.industry Bleomycin hydrolase Cancer Genetic Variation Combination chemotherapy CYSTEINE PROTEASE Middle Aged Neoplasms Germ Cell and Embryonal medicine.disease Prognosis TUMORS Survival Rate Cysteine Endopeptidases Oncology chemistry COOPERATIVE-ONCOLOGY-GROUP Pharmacogenetics ETOPOSIDE Immunology Cancer research Regression Analysis business INDUCED PULMONARY TOXICITY RESISTANCE medicine.drug |
| Zdroj: | Journal of Clinical Oncology, 26(11), 1817-1823. AMER SOC CLINICAL ONCOLOGY |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose Response to chemotherapy may be determined by gene polymorphisms involved in metabolism of cytotoxic drugs. A plausible candidate is the gene for bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, an essential component of chemotherapy regimens for disseminated testicular germ-cell cancer (TC). We investigated whether the single nucleotide polymorphism (SNP) A1450G of the BLMH gene (rs1050565) is associated with survival. Patients and Methods Data were collected on survival and BLMH genotype of 304 patients with TC treated with bleomycin-containing chemotherapy at the University Medical Center Groningen, the Netherlands, between 1977 and 2003. Survival according to genotype was analyzed using Kaplan-Meier curves with log-rank testing and Cox regression analysis with adjustment for confounders. Results BLMH gene SNP A1450G has a significant effect on TC-related survival (log-rank P = .001). The homozygous variant (G/G) genotype (n = 31) is associated with decreased TC related survival compared with the heterozygous variant (A/G; n = 133) and the wild-type (A/A; n = 140). With Cox regression the G/G genotype proves to be an unfavorable prognostic factor, in addition to the commonly used International Germ Cell Consensus Classification prognosis group, with a hazard ratio of 4.97 (95% CI, 2.17 to 11.39) for TC-related death. Furthermore, the G/G genotype shows a higher prevalence of early relapses. Conclusion The homozygous variant G/G of BLMH gene SNP A1450G is associated with reduced survival and higher prevalence of early relapses in TC patients treated with bleomycin-containing chemotherapy. This association is hypothesis generating and may eventually be of value for risk classification and selection for alternative treatment strategies in patients with disseminated TC. |
| Databáze: | OpenAIRE |
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