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. 2013;18(1):80-9.
doi: 10.1634/theoncologist.2012-0291. Epub 2013 Jan 8.

Interleukin-10 gene polymorphisms are associated with freedom from treatment failure for patients with Hodgkin lymphoma

Nils Schoof  1 , Jeremy Franklin, Robert Fürst, Thomas Zander, Frederike von Bonin, Frederic Peyrade, Lorenz Trümper, Volker Diehl, Andreas Engert, Dieter Kube, Daniel Re
Affiliations

Interleukin-10 gene polymorphisms are associated with freedom from treatment failure for patients with Hodgkin lymphoma

Nils Schoof et al. Oncologist. 2013.

Abstract

Background: Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by the production of various cytokines possibly involved in immune deregulation. Interleukin-10 (IL-10) serum levels have been associated with clinical outcome in patients with HL. Because host genetic variations are known to alter the expression and function of cytokines and their receptors, we investigated whether genetic variations influence clinical outcome of patients with HL.

Methods: A total of 301 patients with HL who were treated within randomized trials by the German Hodgkin Study Group were included in this exploratory retrospective study. Gene variations of IL-10 (IL-10(-597AC), rs1800872; IL-10(-824CT), rs1800871; IL-10(-1087AG), rs1800896; IL-10(-3538AT), rs1800890; IL-10(-6208CG), rs10494879; IL-10(-6752AT), rs6676671; IL-10(-7400InDel)), IL-13 (IL-13(-1069CT), rs1800925; IL-13(Q144R), rs20541), and IL-4R (IL-4R(I75V), rs1805010; IL-4R(Q576R), rs1801275) were genotyped.

Results: Inferior freedom from treatment failure (FFTF) was found in patients harboring the IL-10(-597AA), IL-10(-824TT), or the IL-10(-1087AA) genotype. In contrast, the IL-10(-1087G-824C-597C) haplotype present in about 48% of analyzed HL patients is nominally significant for a better FFTF in a Cox-Regression model accounting for stage and treatment. No associations were observed between the other IL-10 gene variations, IL-13(-1069CT), IL-13(Q144R), IL-4R(I75V), IL-4R(Q576R) and the clinical outcome of patients with HL.

Conclusions: Our study provides further evidence that proximal IL-10 promoter gene variations are associated with clinical course of patients with HL. However, treatment success and survival rates are already at a very high rate, supporting the need to design studies focusing on identification of predictors to reduce the side effects of therapy.

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Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1.
Figure 1.
Haplotypes of the analyzed gene variations in the interleukin-10 gene 5′-flanking region. The haplotype frequencies were estimated using the PHASE software applied to the patient cohort (n = 310) of the present study.
Figure 2.
Figure 2.
Freedom from treatment failure (FFTF) probabilities in patients with Hodgkin lymphoma in relation to interleukin (IL)-10 gene variations IL-10−597 (A) and IL-10−1087 (B). (A) Comparison of patients homozygous for IL-10−597A with other genotypes revealed a lower FFTF rate for the homozygous carrier (p = .026). (B) Patients characterized by IL-10−1087AA had also a worse FFTF rate compared to other genotypes (p = .033). For 2-year FFTF rates, see Table 2. Abbreviations: FFTF, freedom from treatment failure; IL, interleukin.
Figure 3.
Figure 3.
Freedom from treatment failure (FFTF) probabilities in patients with Hodgkin lymphoma in relation to proximal interleukin (IL)-10 haplotypes formed by IL-10 SNPs IL-10−1087AG, IL-10−824CT, IL-10−597AC. (A) Patients homozygous for the ATA, ACC, GCC and heterozygous patients (other) differ in FFTF rates (p = .027). (B) Patients with the GCC haplotype (n = 222) showed a lower risk of FFTF compared to non-GCC haplotype carriers (n = 79; p = .033). This result remained nominally significant in a multivariate analysis adjusted to stage and therapy (p = .028). Abbreviations: FFTF, freedom from treatment failure; IL, interleukin.
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