title: NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first line-treated multiple myeloma.
abstract: Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 -94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression-free survival (PFS) was 790 (659-921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515-733) d in deletion-carriers (I/D&D/D, n = 196, P = 0·013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0·622 (0·457-0·847), P = 0·003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703-1101) and 580 (343-817), P = 0·008] than I/D&D/D patients [PFS 659 (487-831) and 488 (323-653), P = 0·531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454-824) and 650 (458-842), P = 0·226], while it was clear in I/I patients [PFS 1140 (803-1477) and 580 (408-752), P < 0·001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 -94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele.
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Varga
authors.forename: Gábor
authors.initials: G
authors.lastname: Mikala
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Andrikovics
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koszarska
authors.forename: Katalin
authors.initials: K
authors.lastname: Balassa
authors.forename: Emma
authors.initials: E
authors.lastname: Ádám
authors.forename: András
authors.initials: A
authors.lastname: Kozma
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
authors.forename: Tamás
authors.initials: T
authors.lastname: Masszi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D018572:Disease-Free Survival; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D011110:Polymorphism, Genetic; D011719:Pyrazines / Q000008:administration & dosage*; D012189:Retrospective Studies; D017384:Sequence Deletion; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001897:Boronic Acids; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D011719:Pyrazines; D000069286:Bortezomib
keywords: NFKB1; bortezomib; multiple myeloma; nuclear factor kappa B; polymorphism