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Annals of Oncology Advance Access published online on June 10, 2009
Annals of Oncology, doi:10.1093/annonc/mdp110
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Favorable impact of the interleukin-4 receptor allelic variant I75 on the survival of diffuse large B-cell lymphoma patients demonstrated in a large prospective clinical trial

N. Schoof1,*, F. von Bonin1, S. Zeynalova2, M. Ziepert2, W. Jung1, M. Loeffler2, M. Pfreundschuh3, L. Trümper1 and D. Kube1

1 Department of Hematology and Oncology, Medical Center of the Georg-August-University of Göttingen, Göttingen
2 Department of Statistics and Epidemiology, Institute of Medical Informatics, University of Leipzig, Leipzig
3 Department of Internal Medicine I, Saarland University, Homburg/Saar, Germany for the DSHNHL (German High-Grade Non-Hodgkin's Lymphoma Study Group)

* Correspondence to: Dr Nils Schoof, Universitätsmedizin der Georg-August-Universität Göttingen, Zentrum für Innere Medizin, Abteilung Hämatologie und Onkologie, 37099 Göttingen, Germany. Tel: +49-0-551-39-8572; Fax: +49-0-551-39-10497; E-mail: nschoof{at}gwdg.de

Background: Recently published data indicate that host germline variations in immune genes can influence the outcome of lymphoma patients. Interleukin (IL)-4 and IL13 are crucial immune factors and may influence the course of the disease. Both cytokines signal through the interleukin-4 receptor (IL4R). Therefore, we investigated whether polymorphisms of IL4, IL13 and IL4R genes could predict the outcome of diffuse large B-cell lymphoma (DLBCL) patients.

Methods: In 228 DLBCL samples of the German High-Grade Non-Hodgkin's Lymphoma Study Group, the polymorphisms of IL4 (-524CT, rs2243250), IL13 (-1069CT, rs1800925) and IL4R (I75V, rs1805010; S503P, rs1805015; Q576R, rs1801275) were analyzed and the soluble interleukin-4 receptor (sIL4R) serum level was measured before the start of chemotherapy.

Results: Patients harboring IL4R V75 (IL4RI75V-AG and IL4RI75V-GG) had shorter overall survival (OS) (P = 0.044) and event-free survival (EFS) (P = 0.056) periods compared with I75 carriers (IL4RI75V-AA). Multivariate analysis adjusted to the International Prognostic Index revealed a relative risk of 1.9 for carriers of the IL4R V75 (P = 0.011) in relation to OS. DLBCL patients homozygous for the IL4R I75 and low sIL4R serum levels have the most favorable OS and EFS.

Conclusions: These data support the role for host germline gene variations of immunologically important factors like the IL4R I75V gene variation to predict the survival in DLBCL patients.

cytokines, DLBCL, IL4R, polymorphism, sIL4R

Received for publication December 27, 2008. Accepted for publication February 2, 2009.


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