Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with epithelial ovarian cancer

Hum Immunol. 2014 Jun;75(6):508-13. doi: 10.1016/j.humimm.2014.04.002. Epub 2014 Apr 19.

Abstract

Killer immunoglobulin-like receptors (KIRs) regulate function of NK cells and subsets of T cells. HLA class I molecules are ligands for inhibitory KIRs while specificity of activating KIRs is mainly unknown. Both KIR and HLA genotypes are highly polymorphic. In this study we analyzed associations of KIR and KIR ligand genes with the incidence and clinical course of epithelial ovarian cancer. DNA of 142 patients was analyzed for KIR genes and 103 samples were typed for HLA class I. Control group consisted of 200 healthy individuals, including 83 women, analyzed separately. The frequency of KIR genes in patients and controls were comparable. HLA-C group 1 (ligand for KIR2DL2/3) was more frequent in patients than in controls (86.4% vs. 67.5%, p=0.002). The frequency of KIR2DS4fl was higher in patients with endometrioid cancer (72.3%) compared with other histological subtypes (36.5%, p=0.004) and controls (29.5%, p=0.0001). KIR and KIR ligand genotype did not influence significantly the clinical course of the disease. We conclude that the genotype of KIR ligands is strongly associated with the incidence of epithelial ovarian cancer while KIR2DS4fl confers susceptibility to endometrioid subtype of the disease.

Keywords: Human leukocyte antigen; KIR2DS4; Killer immunoglobulin-like receptor; NK cells; Ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / immunology
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Carcinoma, Endometrioid / genetics*
  • Carcinoma, Endometrioid / immunology
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / immunology
  • Cystadenocarcinoma, Serous / pathology
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-C Antigens / genetics*
  • HLA-C Antigens / immunology
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / pathology
  • Ligands
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / immunology
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Receptors, KIR / genetics
  • Receptors, KIR / immunology
  • Receptors, KIR2DL2 / genetics*
  • Receptors, KIR2DL2 / immunology
  • Receptors, KIR2DL3 / genetics
  • Receptors, KIR2DL3 / immunology

Substances

  • HLA-C Antigens
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • KIR2DS4 protein, human
  • Ligands
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3