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Annals of Oncology Advance Access originally published online on June 10, 2009
Annals of Oncology 2009 20(9):1548-1554; 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

hematologic malignancies

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.

Key words: cytokines, DLBCL, IL4R, polymorphism, sIL4R

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


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