Association of SNPs in P-glycoprotein 1 with Longer Time to
Event in Bortezomib-treated Multiple Myeloma Patients

a 2013

Association of SNPs in P-glycoprotein 1 with Longer Time to Event in Bortezomib-treated Multiple Myeloma Patients

ALMAŠI, Martina, Barbora SÁBLÍKOVÁ, Lenka KUBICZKOVÁ, Sabina ŠEVČÍKOVÁ, Fedor KRYUKOV et. al.

Základní údaje

Originální název

Association of SNPs in P-glycoprotein 1 with Longer Time to Event in Bortezomib-treated Multiple Myeloma Patients

Autoři

Vydání

14th International Myeloma Workshop, 2013

Další údaje

Jazyk

čeština

Typ výsledku

Konferenční abstrakt

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 1.929

Organizační jednotka

Lékařská fakulta

ISSN

Změněno: 20. 5. 2013 12:41, Mgr. Anna Potáčová, Ph.D.

Anotace

V originále

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.

Návaznosti

NT11154, projekt VaV

Název: Úloha mitotické disrupce v B lymfocytech u mnohočetném myelomu

Investor: Ministerstvo zdravotnictví ČR, Úloha mitotické disrupce v B lymfocytech u mnohočetného myelomu

NT13190, projekt VaV

Název: Molekulární charakteristika centrozomálních abnormalit a jejich prognostický význam pro pacienty s mnohočetným myelomem

Investor: Ministerstvo zdravotnictví ČR, Molekulární charakteristika centrozomálních abnormalit a jejich prognostický význam pro pacienty s mnohočetným myelomem

Citovat

ALMAŠI, Martina, Barbora SÁBLÍKOVÁ, Lenka KUBICZKOVÁ, Sabina ŠEVČÍKOVÁ, Fedor KRYUKOV, Lucie BROŽOVÁ, Jiří JARKOVSKÝ, Michal JURAJDA, Zdeněk ADAM, Z. ŠTEFANIKOVÁ, Miroslav PENKA, Anna VAŠKŮ a Roman HÁJEK. Association of SNPs in P-glycoprotein 1 with Longer Time to Event in Bortezomib-treated Multiple Myeloma Patients. In 14th International Myeloma Workshop. 2013. ISSN 2152-2650.

@proceedings{1107536,
   author = {Almaši, Martina and Sáblíková, Barbora and Kubiczková, Lenka and Ševčíková, Sabina and Kryukov, Fedor and Brožová, Lucie and Jarkovský, Jiří and Jurajda, Michal and Adam, Zdeněk and Štefaniková, Z. and Penka, Miroslav and Vašků, Anna and Hájek, Roman},
   booktitle = {14th International Myeloma Workshop},
   language = {cze},
   title = {Association of SNPs in P-glycoprotein 1 with Longer Time to Event in Bortezomib-treated Multiple Myeloma Patients},
   year = {2013}
}

TY  - CONF
ID  - 1107536
AU  - Almaši, Martina - Sáblíková, Barbora - Kubiczková, Lenka - Ševčíková, Sabina - Kryukov, Fedor - Brožová, Lucie - Jarkovský, Jiří - Jurajda, Michal - Adam, Zdeněk - Štefaniková, Z. - Penka, Miroslav - Vašků, Anna - Hájek, Roman
PY  - 2013
TI  - Association of SNPs in P-glycoprotein 1 with Longer Time to Event in Bortezomib-treated Multiple Myeloma Patients
N2  - 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.
ER  -

ALMAŠI, Martina, Barbora SÁBLÍKOVÁ, Lenka KUBICZKOVÁ, Sabina ŠEVČÍKOVÁ, Fedor KRYUKOV, Lucie BROŽOVÁ, Jiří JARKOVSKÝ, Michal JURAJDA, Zdeněk ADAM, Z. ŠTEFANIKOVÁ, Miroslav PENKA, Anna VAŠKŮ a Roman HÁJEK. Association of SNPs in P-glycoprotein 1 with Longer Time to Event in Bortezomib-treated Multiple Myeloma Patients. In \textit{14th International Myeloma Workshop}. 2013. ISSN~2152-2650.

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