title: Association of killer cell immunoglobulin-like receptor genes with Hodgkin's lymphoma in a familial study.
abstract: BACKGROUND
  Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study.
  
  
  METHODS
  We included 90 families with 90 HL index cases (age 16-35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families.
  
  
  RESULTS
  Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23-0.85] and 0.42[0.21-0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18-71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells.
  
  
  CONCLUSIONS
  This work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL.
authors.affiliation: Laboratoire de Génétique Humaine des Maladies Infectieuses, INSERM, U550, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Besson
authors.forename: Sophie
authors.initials: S
authors.lastname: Roetynck
authors.forename: Fionnuala
authors.initials: F
authors.lastname: Williams
authors.forename: Laurent
authors.initials: L
authors.lastname: Orsi
authors.forename: Corinne
authors.initials: C
authors.lastname: Amiel
authors.forename: Catherine
authors.initials: C
authors.lastname: Lependeven
authors.forename: Guillemette
authors.initials: G
authors.lastname: Antoni
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferme
authors.forename: Patrice
authors.initials: P
authors.lastname: Carde
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Josette
authors.initials: J
authors.lastname: Brière
authors.forename: Martine
authors.initials: M
authors.lastname: Raphael
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Nicolas
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Clavel
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
mesh_terms: D000293:Adolescent; D000328:Adult; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D005810:Multigene Family; D054340:Receptors, KIR / Q000235:genetics*; D055815:Young Adult
chemical_list: D054340:Receptors, KIR