The influence of platinum pathway polymorphisms on the outcome in patients with malignant mesothelioma
| Autor: | Viljem Kovac, Vita Dolžan, Julija Hmeljak, Nina Erčulj |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Oncology
Adult Male Mesothelioma medicine.medical_specialty DNA Repair Bioinformatics Disease-Free Survival Carboplatin GSTP1 Internal medicine Genotype Antineoplastic Combined Chemotherapy Protocols medicine Humans Progression-free survival Genetic Association Studies Aged Glutathione Transferase Proportional Hazards Models Xeroderma Pigmentosum Group D Protein Aged 80 and over Polymorphism Genetic business.industry Haplotype Alopecia Nausea Hematology Leukopenia Sequence Analysis DNA Middle Aged medicine.disease Endonucleases Thrombocytopenia DNA-Binding Proteins Treatment Outcome Haplotypes Toxicity Female ERCC1 Cisplatin business Pharmacogenetics |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 23(4) |
| ISSN: | 1569-8041 |
| Popis: | Background Platinum-based therapy is widely used in the treatment of malignant mesothelioma (MM); however, the efficacy and toxicity of platinum agents vary greatly between patients. The aim of our study was to evaluate the influence of platinum pathway polymorphisms on treatment outcome in patients with MM. Patients and methods In total, 133 patients with MM treated with (n = 97) or without (n = 36) platinum-based therapy were genotyped for common XPD, ERCC1, and GSTP1 polymorphisms, as well as for GSTM1 and GSTT1 gene deletion. Haplotype analysis was carried out to assess the combined effect of nucleotide excision repair (NER) polymorphisms. Results GST polymorphisms were not associated with treatment outcome in patients with MM. In the group of platinum-treated patients with MM, ERCC1 8092C/C wild-type genotype significantly influenced progression-free survival (PFS) in multivariable analysis accounting for clinical variables (P = 0.034). XPD 312Asp/Asp and ERCC1 8092C/C wild-type genotypes also increased the odds of treatment-related toxic effects in univariable as well as multivariable analysis. The association of wild-type NER genotypes with better PFS and higher susceptibility to treatment-related toxic effects was confirmed in haplotype analysis. Conclusions Our results suggest that polymorphisms in NER pathway influence platinum-treatment efficacy and toxicity; therefore, these should be further evaluated as potential markers for the prediction of clinical outcome in patients with MM. |
| Databáze: | OpenAIRE |
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