title: Polymorphisms in the interleukin 10 gene promoter are associated with susceptibility to aggressive non-Hodgkin's lymphoma.
abstract: Interleukin-10 (IL-10) is mainly an anti-inflammatory cytokine produced by a number of cells including normal and neoplastic B cells. It has been implicated in autoimmunity, transplantation tolerance and tumourigenesis. Polymorphisms in the IL-10 gene promoter genetically determine inter-individual differences in IL-10 production. The aim of this study was to determine whether polymorphisms in the IL-10 gene promoter play a role in predisposing an individual to lymphoma. We analysed the frequencies of three single base substitutions in the IL-10 promoter in patients with aggressive lymphoma (B-cell DLCL n = 46, other aggressive histologies n = 17), Hodgkin's disease (n = 44) or low/intermediate grade lymphoma (n = 46), compared to healthy controls. The frequency of the low-IL-10 producing AA allele (at position -1082) was significantly higher in patients with aggressive lymphoma compared to controls (p = 0.0344, Odds ratio 1.974, 95% C.I 1.066-3.655). Similarly, the frequency of the low IL-10 producing ATA or the intermediate-IL-10- producing ACC haplotype was significantly higher in patients with aggressive disease compared to controls (p = 0.0255, Odds ratio 1.647, 95% C.I 1.077-2.518). No association was found between IL-10 genotypes and Hodgkin's disease or less aggressive forms of lymphoma. Thus, polymorphisms in the IL-10 gene promoter which are associated with a low IL-10 producing phenotype may influence susceptibility to aggressive forms of lymphoma or may contribute to the pathogenesis of this disease.
authors.affiliation: The Western Australian Centre for Pathology and Medical Research, Perth, WA, Australia.
authors.forename: L M
authors.initials: LM
authors.lastname: Cunningham
authors.forename: C
authors.initials: C
authors.lastname: Chapman
authors.forename: R
authors.initials: R
authors.lastname: Dunstan
authors.forename: M C
authors.initials: MC
authors.lastname: Bell
authors.forename: D J L
authors.initials: DJ
authors.lastname: Joske
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D016753:Interleukin-10