title: Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with epithelial ovarian cancer.
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.
authors.affiliation: Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland. Electronic address: sgiebel@io.gliwice.pl.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.affiliation: Department of Clinical and Experimental Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Boratyn-Nowicka
authors.affiliation: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland; Department and Clinic of Urology, Medical University Wroclaw, Wroclaw, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Karabon
authors.affiliation: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jedynak
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Pamula-Pilat
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Tecza
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kula
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kowal
authors.affiliation: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Grzybowska
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology; D054343:Receptors, KIR2DL2 / Q000235:genetics* / Q000276:immunology; D054344:Receptors, KIR2DL3 / Q000235:genetics / Q000276:immunology
chemical_list: D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; C473953:KIR2DS4 protein, human; D008024:Ligands; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3
keywords: Human leukocyte antigen; KIR2DS4; Killer immunoglobulin-like receptor; NK cells; Ovarian cancer