Effect of interleukin-10 gene polymorphisms on clinical outcome of patients with aggressive non-Hodgkin's lymphoma: an exploratory study.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Department of Hematology and Oncology and Pharmacology, Medical School of the Georg-August-University, Göttingen, Germany. dkube@gwdg.de
Dieter
D
Kube
Thanh-Duc
TD
Hua
Frederike
F
von Bonin
Nils
N
Schoof
Samira
S
Zeynalova
Marita
M
Klöss
Daniela
D
Gocht
Bernd
B
Potthoff
Mladen
M
Tzvetkov
Jürgen
J
Brockmöller
Markus
M
Löffler
Michael
M
Pfreundschuh
Lorenz
L
Trümper
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016896:Treatment Outcome
D016753:Interleukin-10