title: 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 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.affiliation: Department of Hematology and Oncology, Medical Center of the Georg-August-University Göttingen, 37099 Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Schoof
authors.forename: Jeremy
authors.initials: J
authors.lastname: Franklin
authors.forename: Robert
authors.initials: R
authors.lastname: Fürst
authors.forename: Thomas
authors.initials: T
authors.lastname: Zander
authors.forename: Frederike
authors.initials: F
authors.lastname: von Bonin
authors.forename: Frederic
authors.initials: F
authors.lastname: Peyrade
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Volker
authors.initials: V
authors.lastname: Diehl
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.forename: Dieter
authors.initials: D
authors.lastname: Kube
authors.forename: Daniel
authors.initials: D
authors.lastname: Re
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006689:Hodgkin Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D017211:Treatment Failure
chemical_list: D016753:Interleukin-10