Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

Annette Juul Vangsted, Tobias Wirenfeldt Klausen, Niels Abildgaard, Niels Frost Andersen, Peter Gimsing, Henrik Gregersen, Bjørn Andersen Nexø, Ulla Vogel

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Little is known on the impact of polymorphisms in the IL1B gene on outcome in multiple myeloma. In a population-based study of 348 Danish myeloma patients treated with high-dose treatment (HDT), 146 patients treated with INF-alpha maintenance treatment, and in 243 patients with relapse, we analysed the impact on outcome of HDT, INF-alpha maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (-3737(T), -1464(G) and -31(T)), giving high IL1B promoter activity, were associated with longer time-to-treatment failure (TTF) (HR, 1.4 (1.0-1.9) and 1.5 (1.1-2.0)) and overall survival (HR, 1.8 (1.2-2.6) and 1.6 (1.1-2.3)) after HDT. Among INF-alpha treated patients, a trend towards better TTF was found in patients carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1-2.4)). Furthermore, among INF-alpha treated patients, gene-gene interaction studies on IL1B C-3737T and NFDeB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (-3737(T), -1464(G) and -31(T)) benefit from a better outcome of HDT and INF-alpha treatment, an effect that may be related to the NF-kappa B pathway
    OriginalsprogEngelsk
    TidsskriftAnnals of Hematology
    Vol/bind90
    Udgave nummer10
    Sider (fra-til)1173-1181
    ISSN0939-5555
    DOI
    StatusUdgivet - 2011

    Citer dette

    Vangsted, Annette Juul ; Klausen, Tobias Wirenfeldt ; Abildgaard, Niels ; Andersen, Niels Frost ; Gimsing, Peter ; Gregersen, Henrik ; Nexø, Bjørn Andersen ; Vogel, Ulla. / Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib. I: Annals of Hematology. 2011 ; Bind 90, Nr. 10. s. 1173-1181 .
    @article{49f1ba1d4bb74bd6b8bf241eb329252e,
    title = "Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib",
    abstract = "Little is known on the impact of polymorphisms in the IL1B gene on outcome in multiple myeloma. In a population-based study of 348 Danish myeloma patients treated with high-dose treatment (HDT), 146 patients treated with INF-alpha maintenance treatment, and in 243 patients with relapse, we analysed the impact on outcome of HDT, INF-alpha maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (-3737(T), -1464(G) and -31(T)), giving high IL1B promoter activity, were associated with longer time-to-treatment failure (TTF) (HR, 1.4 (1.0-1.9) and 1.5 (1.1-2.0)) and overall survival (HR, 1.8 (1.2-2.6) and 1.6 (1.1-2.3)) after HDT. Among INF-alpha treated patients, a trend towards better TTF was found in patients carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1-2.4)). Furthermore, among INF-alpha treated patients, gene-gene interaction studies on IL1B C-3737T and NFDeB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (-3737(T), -1464(G) and -31(T)) benefit from a better outcome of HDT and INF-alpha treatment, an effect that may be related to the NF-kappa B pathway",
    keywords = "Multiple myeloma, IL1B, Haplotype and outcome",
    author = "Vangsted, {Annette Juul} and Klausen, {Tobias Wirenfeldt} and Niels Abildgaard and Andersen, {Niels Frost} and Peter Gimsing and Henrik Gregersen and Nex{\o}, {Bj{\o}rn Andersen} and Ulla Vogel",
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    doi = "10.1007/s00277-011-1194-3",
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    Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib. / Vangsted, Annette Juul; Klausen, Tobias Wirenfeldt; Abildgaard, Niels; Andersen, Niels Frost; Gimsing, Peter; Gregersen, Henrik; Nexø, Bjørn Andersen; Vogel, Ulla.

    I: Annals of Hematology, Bind 90, Nr. 10, 2011, s. 1173-1181 .

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    AU - Vangsted, Annette Juul

    AU - Klausen, Tobias Wirenfeldt

    AU - Abildgaard, Niels

    AU - Andersen, Niels Frost

    AU - Gimsing, Peter

    AU - Gregersen, Henrik

    AU - Nexø, Bjørn Andersen

    AU - Vogel, Ulla

    PY - 2011

    Y1 - 2011

    N2 - Little is known on the impact of polymorphisms in the IL1B gene on outcome in multiple myeloma. In a population-based study of 348 Danish myeloma patients treated with high-dose treatment (HDT), 146 patients treated with INF-alpha maintenance treatment, and in 243 patients with relapse, we analysed the impact on outcome of HDT, INF-alpha maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (-3737(T), -1464(G) and -31(T)), giving high IL1B promoter activity, were associated with longer time-to-treatment failure (TTF) (HR, 1.4 (1.0-1.9) and 1.5 (1.1-2.0)) and overall survival (HR, 1.8 (1.2-2.6) and 1.6 (1.1-2.3)) after HDT. Among INF-alpha treated patients, a trend towards better TTF was found in patients carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1-2.4)). Furthermore, among INF-alpha treated patients, gene-gene interaction studies on IL1B C-3737T and NFDeB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (-3737(T), -1464(G) and -31(T)) benefit from a better outcome of HDT and INF-alpha treatment, an effect that may be related to the NF-kappa B pathway

    AB - Little is known on the impact of polymorphisms in the IL1B gene on outcome in multiple myeloma. In a population-based study of 348 Danish myeloma patients treated with high-dose treatment (HDT), 146 patients treated with INF-alpha maintenance treatment, and in 243 patients with relapse, we analysed the impact on outcome of HDT, INF-alpha maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (-3737(T), -1464(G) and -31(T)), giving high IL1B promoter activity, were associated with longer time-to-treatment failure (TTF) (HR, 1.4 (1.0-1.9) and 1.5 (1.1-2.0)) and overall survival (HR, 1.8 (1.2-2.6) and 1.6 (1.1-2.3)) after HDT. Among INF-alpha treated patients, a trend towards better TTF was found in patients carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1-2.4)). Furthermore, among INF-alpha treated patients, gene-gene interaction studies on IL1B C-3737T and NFDeB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (-3737(T), -1464(G) and -31(T)) benefit from a better outcome of HDT and INF-alpha treatment, an effect that may be related to the NF-kappa B pathway

    KW - Multiple myeloma

    KW - IL1B

    KW - Haplotype and outcome

    U2 - 10.1007/s00277-011-1194-3

    DO - 10.1007/s00277-011-1194-3

    M3 - Journal article

    VL - 90

    SP - 1173

    EP - 1181

    JO - Annals of Hematology

    JF - Annals of Hematology

    SN - 0939-5555

    IS - 10

    ER -