This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kube, D. Articles by Trümper, L. PubMed PubMed Citation Articles by Kube, D. Articles by Trümper, L.

Effect of Interleukin-10 Gene Polymorphisms on Clinical Outcome of Patients with Aggressive Non-Hodgkin's Lymphoma: An Exploratory Study

Authors' Affiliations: Departments of ¹ Hematology and Oncology and ² Pharmacology and Toxicology, Medical School of the Georg-August-University, Göttingen, Germany; ³ University of Leipzig, Institute of Medical Informatics, Statistics and Epidemiology, Leipzig, Germany; ⁴ Department of Internal Medicine I, Saarland University, Homburg/Saar for the German High-Grade NHL Study Group, Homburg/Saar, Germany

Requests for reprints: Dieter Kube, Universitätsmedizin der Georg-August-Universität Göttingen, Zentrum für Innere Medizin, Abteilung Hämatologie und Onkologie, 37099 Göttingen, Germany. Phone: 49-551-395307; Fax: 49-551-398587; E-mail: dkube{at}gwdg.de.

Purpose: Current chemotherapy can achieve high response rates in aggressive non-Hodgkin's lymphoma (NHL), but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis whether interleukin-10 (IL-10) polymorphisms predict clinical outcome, leukocytopenia, or infectivity during therapy. IL-10 was chosen because immune alterations are a major risk factor for NHL, and IL-10 is a cytokine involved in inflammatory processes associated with clinical outcome.

Experimental Design: Five hundred patients with aggressive NHL treated with CHOP/CHOEP were analyzed for IL-10 gene polymorphisms, including distal loci -7400InDel, -6752AT (rs6676671), and -6208CG (rs10494879) in comparison with proximal loci -3538AT (rs1800890), -1087AG (rs1800896), and -597AC (rs1800872) according to the incidence and outcome of the lymphoma.

Results: No differences in allele frequencies or haplotypes were found comparing a cohort of patients with aggressive NHL/diffuse large B-cell lymphoma with a healthy control group. Patients with aggressive NHL characterized by IL-10_-7400DelDel had shorter overall survival periods compared with the other genotypes (P = 0.004). The 3-year rate is 43.4% for IL-10_-7400DelDel and 73.4% for IL-10_-7400InIn and IL-10_-7400InDel together. A significant increased risk for event-free survival is found for carriers of the genotype IL-10_{-6752TT-6208CC-3538AA} (P = 0.047). Multivariate analysis of IL-10_-7400 gene variation in relation to overall survival adjusted to international prognostic index revealed a relative risk of 1.9 for carriers of IL-10_-7400DelDel (P = 0.037). No associations were found analyzing diffuse large B-cell lymphoma patients separately.

Conclusion: Our results indicate that IL-10 gene variations could be associated to the clinical course of aggressive NHL, which points out the importance of host factors and respective genetic elements for treatment response.