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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.

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