Interleukin-10 Gene Polymorphisms are Associated With Freedom From Treatment Failure for Patients With Hodgkin Lymphoma

Abstract

Background. Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by the production of various cytokinesImplications for Practice: Inter-individual genetic variations (polymorphisms) of host genes (patient genes) might be associated with different outcomes for cancer patients. This could be independent of the characteristics of the tumor itself. We asked if the course of Hodgkin Lymphoma patients is changed depending on the genetic background of the patient. As Hodgkin Lymphoma is characterized by an inflammatory microenvironment, we studied polymorphisms of three well-selected immune genes by molecular analysis. Our study provides evidence that a genetic variation of the IL-10 gene is associated with a worse clinical outcome in patients with HL. Although clinical practice is not changed based on these data, our study is a proof of concept and should stimulate further research in this area on a whole genome basis.

Macrophage Polarization Reflects T Cell Composition of Tumor Microenvironment in Pediatric Classical Hodgkin Lymphoma and Has Impact on Survival

“…In light of this, CMAF in combination with a macrophage marker (CD68 or CD163) may identify at least a subset of M2-polarized macrophages. Given the importance of IL10 in cHL pathobiology [ 56 – 59 ], we hypothesize that, even if not all M2-polarized macrophages are identified by our approach, CMAF expressing macrophages would represent a biologically significant population in this disease.…”

Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts

“…One study of 184 HL patients (46 in tumor tissue samples) observed an effect of IL10 −592C>A and IL6 −174G>C for freedom from treatment failure (FFTF), with IL10 −592AA and IL6 −174GG at higher risk of relapse [31]. A recent study on 301 HL patients confirmed the result for the IL10 −592 SNP, showing that patients with IL10 −592AA, IL10 −819TT or IL10 −1082AA genotypes had an inferior FFTF [33]. In DLBCL, the prognostic impact of promoter IL10 SNPs is also conflicting [24–28].…”

“…These SNPs were chosen based on i) their localization in regulatory regions of the genes ( IL10, TNFA, IL6, CCL17 ); ii) previous studies showing in vitro functional effect of these SNPs on cytokine expression [17, 39]; iii) previous lymphoma studies showing that these SNPs might predict clinical outcome [23–33]. …”

“…Five studies have explored the prognostic value of SNPs in IL6, TNFA and IL10 genes [28, 30–33], with conflicting results for IL6 −174G>C SNP [30, 31], consistent results for IL10 −1082A>G and IL10 −592>A SNPs [31, 33], and no association for the IL10 −3575T>A SNP [28, 33] or the TNFA, IL13 and IL4R SNPs [31, 33]. Herein, we investigated the association of cytokine gene polymorphisms in IL10, TNFA, IL6, IL1RN, INFG and CCL17 with cytokine levels and patient outcome in two independent cohorts of CHL patients.…”

Glutathione S-transferase M1-T1 null genotypes and susceptibility to Hodgkin’s lymphoma

“…Studying genetic susceptibility to the HL can lead to clarifying of its mechanism and risk estimation among the population. Several studies have examined polymorphisms in some genes and cancer risk especially HL, such as cytokines genes (IL6,TNFA,IL10,L1RN,INFG,CCL17 and TGFB) (DOMINGO-DOMÈNECH et al, 2007;CORDANO et al, 2005;HOHAUS et al, 2007;SCHOOF et al, 2013;GHESQUIÈRES et al, 2013;DEHGHAN TEZERJANI et al, 2015) and HLA genes (HUANG et al, 2012). The associations between GST genes variants and HL has also investigated (HOHAUS et al, 2003).…”