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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3529-3534.
Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-06-1850.
Submitted June 11, 2003
Accepted December 29, 2003
The interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma
Ewa Lech-Maranda, Lucile Baseggio, Jacques Bienvenu, Carole Charlot, Francoise Berger, Dominique Rigal, Krzystof Warzocha, Bertrand Coiffier, and Gilles Salles*
Equipe d'Accueil 3738 <<Pathologie des Cellules Lymphoides>>, Universite Claude Bernard, Lyon, France, Lyon, France; Department of Hematology, Medical University of Lodz, Lodz, Poland
Equipe d'Accueil 3738 <<Pathologie des Cellules Lymphoides>>, Universite Claude Bernard, Lyon, France, Lyon, France
Equipe d'Accueil 3738 <<Pathologie des Cellules Lymphoides>>, Universite Claude Bernard, Lyon, France, Lyon, France; Laboratoire d'Immunologie, Centre Hospitalier Lyon-Sud, Pierre-Benite, France
Equipe d'Accueil 3738 <<Pathologie des Cellules Lymphoides>>, Universite Claude Bernard, Lyon, France, Lyon, France; Service d'Anatomie Pathologique, Centre Hospitalier Lyon-Sud, Pierre-Benite, France
Equipe d'Accueil 3738 <<Pathologie des Cellules Lymphoides>>, Universite Claude Bernard, Lyon, France, Lyon, France; Etablissement Francais du Sang, Lyon, France
Institute of Hematology and Blood Transfusion, Warsaw, Poland
Equipe d'Accueil 3738 <<Pathologie des Cellules Lymphoides>>, Universite Claude Bernard, Lyon, France, Lyon, France; Service d'Hematologie, Centre Hospitalier Lyon-Sud, Pierre-Benite, France
* Corresponding author; email: gilles.salles{at}chu-lyon.fr.
The aim of the study was to investigate whether interleukin-10 (IL-10) genetic polymorphisms influence this cytokine production as well as the incidence and outcome of diffuse large B-cell lymphoma (DLBCL). The frequency of IL-10-1082G allele was found to be higher in 199 DLBCL patients as compared to 112 controls (0.47 versus 0.39, P=.043). Increased serum levels of IL-10 was associated with adverse prognostic factors and poor DLBCL outcome. The frequencies of IL-10-819T and IL-10-592A alleles were lower in patients with elevated IL-10 serum levels (0.155 versus 0.32, P=0.14). As compared to patients carrying the IL-10-1082AA genotype, those with the IL-10-1082G allele (IL-10-1082GG/GA genotypes) had higher complete remission rate (78% [CI 71%-85%] versus 65% [CI 52%-78%], P=.07), 5-years freedom from progression (FFP) (60% [CI 52%-68%] versus 40% [CI 27%-53%], P=.013) and overall survival (OS) (63% [CI 55%-71%] versus 33% [CI 20%-45%], P=.0009). Among factors of the International Prognostic Index, IL-10-1082G allele remained an independent variable predicting longer FFP (RR [relative risk]=.76, P=.00035) and OS (RR=.78, P=.0015). These results indicate that IL-10 production contributes to the clinical course of DLBCL and that this phenomenon involves a substantial genetic component.
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