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.
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.
Authors: A H Sarris; K O Kliche; P Pethambaram; A Preti; S Tucker; C Jackow; O Messina; W Pugh; F B Hagemeister; P McLaughlin; M A Rodriguez; J Romaguera; H Fritsche; T Witzig; M Duvic; M Andreeff; F Cabanillas Journal: Ann Oncol Date: 1999-04 Impact factor: 32.976
Authors: J Eskdale; G Gallagher; C L Verweij; V Keijsers; R G Westendorp; T W Huizinga Journal: Proc Natl Acad Sci U S A Date: 1998-08-04 Impact factor: 11.205
Authors: R Bacchetta; M Bigler; J L Touraine; R Parkman; P A Tovo; J Abrams; R de Waal Malefyt; J E de Vries; M G Roncarolo Journal: J Exp Med Date: 1994-02-01 Impact factor: 14.307
Authors: Hervé Ghesquières; Matthew J Maurer; Olivier Casasnovas; Stephen M Ansell; Beth R Larrabee; Eva Lech-Maranda; Anne J Novak; Anne-Laure Borrel; Susan L Slager; Pauline Brice; Cristine Allmer; Annie Brion; Steven C Ziesmer; Franck Morschhauser; Thomas M Habermann; Isabelle Gaillard; Brian K Link; Aspasia Stamatoullas; Christophe Fermé; Ahmet Dogan; William R Macon; Josée Audouin; James R Cerhan; Gilles Salles Journal: Cytokine Date: 2013-09-03 Impact factor: 3.861