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.
Kube
Dieter
D
Department of Hematology and Oncology and Pharmacology, Medical School of the Georg-August-University, Göttingen, Germany. dkube@gwdg.de
Hua
Thanh-Duc
TD
von Bonin
Frederike
F
Schoof
Nils
N
Zeynalova
Samira
S
Klöss
Marita
M
Gocht
Daniela
D
Potthoff
Bernd
B
Tzvetkov
Mladen
M
Brockmöller
Jürgen
J
Löffler
Markus
M
Pfreundschuh
Michael
M
Trümper
Lorenz
L
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