Polymorphisms of nuclear factor-κB family genes are associated with development of multiple myeloma and treatment outcome in patients receiving bortezomib-based regimens.
Haematologica
; 96(5): 729-37, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21228035
ABSTRACT
BACKGROUND:
The nuclear factor-κB pathway is an important signaling pathway activated in multiple myeloma cells. Bortezomib inhibits nuclear factor-κB activation and is an important antimyeloma agent. Nevertheless, patients treated with this drug eventually relapse. We hypothesized that the nuclear factor-κB pathway may be associated with multiple myeloma and patients' responses to bortezomib. DESIGN ANDMETHODS:
In this study we analyzed 26 polymorphism sites of nuclear factor-κB family member genes, IKBα, NFKB2, and TRAF3, in 527 unrelated Chinese Han subjects (252 with multiple myeloma and 275 controls) using a Sequenom MassARRAY genotyping assay, and examined the outcome of 83 patients treated with a bortezomib-based regimen.RESULTS:
Single nucleotide polymorphisms in the TRAF3 rs12147254 A allele and a specific haplotype 1 of TRAF3 [GAACAG] are associated with a decreased risk of multiple myeloma (odds ratio 0.709, P<0.001, and odds ratio 0.543, P<0.0001), while TRAF3 haplotype 4 [GGACAG] was associated with an increased risk of development of multiple myeloma (odds ratio 2.099, P=0.001). Moreover, the TRAF3 rs11160707 GA+AA genotype was significantly associated with a better progression-free survival (P=0.018). Patients with the NFKB2 rs12769316 GA+AA genotype had a superior overall survival (P=0.020), while those with the rs1056890 CT+TT genotype had an inferior overall survival (P=0.037). In an exploratory analysis, patients with the GA+AA/CC/GG genotype at the rs12769316, rs1056890, and rs11160707 sites had a significantly superior overall survival compared to patients with a wild-type genotype (P=0.007). In the multivariable analysis, TRAF3 rs11160707 was found to be an independent favorable factor for progression-free survival (hazard ratio 0.428, P=0.028).CONCLUSIONS:
Nuclear factor-κB family member gene polymorphisms play a role in the development of multiple myeloma and in the response to bortezomib therapy.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
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Mieloma Múltiplo
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article