title: Interleukin-6 plasma levels are modulated by a polymorphism in the NF-κB1 gene and are associated with outcome following rituximab-combined chemotherapy in diffuse large B-cell non-Hodgkin lymphoma.
abstract: Peripheral blood cytokines are known prognostic parameters in diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy, but their role after the introduction of rituximab is unknown. Seven polymorphisms in the promoter regions of IL-6, IL-10 and NF-κB1 genes were assessed in 167 patients with DLBCL and 99 controls and correlated with interleukin-6 (IL-6) and IL-10 plasma levels. Outcome was analyzed in 137 patients treated with rituximab-based chemotherapy. The NF-κB1 - 94ATTG deletion was associated with increased IL-6 and IL-10 in DLBCL. High IL-6 concentration correlated with unfavorable prognostic factors included in the international prognostic index (IPI) and predicted for inferior progression-free (p = 0.007) and overall survival (p = 0.02). IL-6 levels remained a significant outcome predictor also including IPI as a covariate (p = 0.006 for progression-free survival). Our data suggest that the NF-κB1 genetic background influences IL-6 production in DLBCL, and that high IL-6 concentration is an independent prognostic factor also in the "rituximab era."
authors: Istituto di Ematologia, Università Cattolica S. Cuore, Rome, Italy.
authors: Manuela
authors: M
authors: Giachelia
authors: Maria Teresa
authors: MT
authors: Voso
authors: Maria Chiara
authors: MC
authors: Tisi
authors: Maurizio
authors: M
authors: Martini
authors: Valentina
authors: V
authors: Bozzoli
authors: Giuseppina
authors: G
authors: Massini
authors: Francesco
authors: F
authors: D'Aló
authors: Luigi Maria
authors: LM
authors: Larocca
authors: Giuseppe
authors: G
authors: Leone
authors: Stefan
authors: S
authors: Hohaus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D000069283:Rituximab; D017384:Sequence Deletion; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D009363:Neoplasm Proteins; D003561:Cytarabine; D016753:Interleukin-10; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D008942:Mitoxantrone; D011241:Prednisone; D008775:Methylprednisolone