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.
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 (IL4R(I75V-AG) and IL4R(I75V-GG)) had shorter overall survival (OS) (P = 0.044) and event-free survival (EFS) (P = 0.056) periods compared with I75 carriers (IL4R(I75V-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.
Schoof
N
N
Department of Hematology and Oncology, Medical Center of the Georg-August-University of Göttingen, Göttingen. Electronic address: nschoof@gwdg.de.
von Bonin
F
F
Department of Hematology and Oncology, Medical Center of the Georg-August-University of Göttingen, Göttingen.
Zeynalova
S
S
Department of Statistics and Epidemiology, Institute of Medical Informatics, University of Leipzig, Leipzig.
Ziepert
M
M
Department of Statistics and Epidemiology, Institute of Medical Informatics, University of Leipzig, Leipzig.
Jung
W
W
Department of Hematology and Oncology, Medical Center of the Georg-August-University of Göttingen, Göttingen.
Loeffler
M
M
Department of Statistics and Epidemiology, Institute of Medical Informatics, University of Leipzig, Leipzig.
Pfreundschuh
M
M
Department of Internal Medicine I, Saarland University, Homburg/Saar, Germany for the DSHNHL (German High-Grade Non-Hodgkin's Lymphoma Study Group).
Trümper
L
L
Department of Hematology and Oncology, Medical Center of the Georg-August-University of Göttingen, Göttingen.
Kube
D
D
Department of Hematology and Oncology, Medical Center of the Georg-August-University of Göttingen, Göttingen.
D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000097:blood / Q000235:genetics*; D055815:Young Adult
D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4