Association of SNPs in P-glycoprotein 1 with Longer Time to Event in Bortezomib-treated Multiple Myeloma Patients
| Autoři | |
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| Rok publikování | 2013 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Single nucleotide polymorphisms (SNPs) in P-glycoprotein 1 (MDR1) and multiple drug resistance protein 1 (MRP1) genes may mediate drug resistance. Therefore, association of three SNPs and their haplotypes in MDR1 and one in MRP1 gene (rs4148356) with outcomes in patients (pts) with multiple myeloma (MM) was evaluated. Methods: In total, 235 MM pts (112F/123M) was included in our study. All pts underwent bortezomib-based treatment in these treatment lines: 1st (20.4%; 48/235), 2nd (40.9%; 96/235), 3rd (28.9%; 68/235), 4th (7.7%; 18/235), over 5th line (2.1%; 5/235). Regimen CVD-cyclophosphamide, Velcade (bortezomib), dexamethasone was used in 63.8% (150/235) of pts. Genotypes were determined using TaqMan real-time PCR allelic discrimination. Results: All SNPs were in Hardy-Weinberg equilibrium. All pts with no copies of haplotype TGT (rs1045642, rs2032582 and rs1128503) in MDR1 gene had longer time of survival up to 2 years from the beginning of therapy (median 23.1 vs. 11.4 months; p=0.017), longer time of progression-free survival (PFS; median 9.1 vs. 7.5 months; p=0.007) and longer time to progression (TTP; median 13.0 vs. 9.1 months; p=0.017) than pts with one or two copies of this haplotype, no association was found in MRP1 gene. Conclusion: We found significant pharmacogenetic association of specific haplotype in MDR1 gene with two-year outcome of pts with MM treated with bortezomib. Further studies are needed to determine if such data can be used for individualization of the treatment. |
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