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
SN - 0939-5555
VL - 90
SP - 1173
EP - 1181
JO - Annals of Hematology
JF - Annals of Hematology
IS - 10
ER -