Vangsted, Annette J., Klausen, Tobias Wirenfeldt, Gimsing, Peter, Abildgaard, Niels, Andersen, Niels F., Gregersen, Henrik, Nexø, Bjørn Andersen, Vogel, Ulla Birgitte, Department of Oncology and Haematology, Roskilde Hospital, University of Copenhagen = Københavns Universitet (KU), Department of Oncology and Haematology Roskilde Hospital, Department of Haematology, Herlev and Gentofte Hospital, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Odense University Hospital, Aarhus University Hospital, Institute of Human Genetics, National Food Institute, Technical University of Denmark [Lyngby] (DTU), National Research Centre for the Working Environment, and National Research Centre for the Working Environment (NRCWE)
International audience; The gene was originally described as an inhibitor of RelA/p65 subunit of nuclear factor κB (NF-κB). Here, we analyse the association between genetic variation in the genes and and outcome of 348 myeloma patients treated with high-dose treatment (HDT), 146 patients treated with interferon-α (INF-α) as maintenance treatment, 177 patients treated with thalidomide, and 74 patients treated with bortezomib at relapse and address if the effects of polymorphisms in and are modified by a functional polymorphism in . By linkage disequilibrium mapping, we found that variant alleles of several polymorphisms in a sub-region of 19q13.3 spanning the regions -intron1-1 to intron1-3 and the region exon1 to exon3-6 in were associated with prolonged time-to-treatment failure (TTF; = 0.003) and overall survival (OS; = 0.02). Haplotype analyses revealed that none of the haplotypes were more strongly associated to TTF or OS than the two strongly linked SNPs, -intron1-1 (rs4572514) and (rs967591). The association of -intron1-1 and with TTF was independent of -94 ins/del, but homozygous ins-allele carriers which were also variant allele carriers of -intron1-1 or had the longest OS. Among patients treated with INF-α or thalidomide, no effect was seen in relation to genotype. Our results indicate that polymorphism in and are associated with outcome of myeloma patients treated with HDT. Combination analyses with the functional polymorphism in suggest that a possibly functional effect of or could be related to NF-κB availability.