title: Association of the genetic diversity of killer cell immunoglobulin-like receptor genes and HLA-C ligand in Saudi women with breast cancer.
abstract: Breast cancer (BC) progression and metastases have been linked to antitumor immunity inefficiency and particularly to natural killer (NK) cells. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic receptors of NK cells. Through their interactions with human leukocyte antigen (HLA)-C ligands, they modulate NK and T cell actions against target cells. Therefore, we studied the combinatorial effect of KIR genes and their HLA-C ligands on the susceptibility to development of BC in Saudi women. The presence of KIR genes and HLA-C1 and HLA-C2 groups was typed in 50 Saudi patients living in Riyadh and 65 healthy controls using polymerase chain reaction with sequence-specific primers. Our results indicated a protective effect by the KIR2DS2, 2DS3, and 2DL5A genes against BC (OR = 0.25, 0.21, and 0.27, respectively, and p < 0.01). The synergistic action of the three genes was observed when they occurred together, and the absence of the three genes increased BC occurrence by 6.5-fold. Distribution of the HLA-C1/C2 ligand between patients and controls showed an increase in the risk of BC occurrence for the heterozygote C1/C2 (OR = 2.33; 95 % CI = 1.08-5.02; p = 0.037) and a protective effect of the homozygote C2C2 (OR = 0.03; 95 % CI = 0.009-0.098; p < 0.001). Combinatory analyses of KIR genes and their HLA-C ligands showed protective effects of KIR2DL2 and 2DL3 in the absence of their HLA-C1 ligand. These results suggested that KIR-gene content combined with their ligand could influence the risk of BC development in women in Saudi Arabia.
authors.affiliation: Zoology Department, College of Sciences, King Saud University, Post Office Box 2455, Riyadh, 11451, Saudi Arabia.
authors.forename: Suliman Y
authors.initials: SY
authors.lastname: Alomar
authors.affiliation: Zoology Department, College of Sciences, King Saud University, Post Office Box 2455, Riyadh, 11451, Saudi Arabia.
authors.forename: Afrah
authors.initials: A
authors.lastname: Alkhuriji
authors.affiliation: Zoology Department, College of Sciences, King Saud University, Post Office Box 2455, Riyadh, 11451, Saudi Arabia.|Clore Laboratory, Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhyrn
authors.affiliation: Department of Microbiology/Pathology, King Khalid University Hospital, College of Medicine King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdulkarim
authors.initials: A
authors.lastname: Alhetheel
authors.affiliation: Immunology and HLA section, Pathology and Clinical Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Jurayyan
authors.affiliation: Zoology Department, College of Sciences, King Saud University, Post Office Box 2455, Riyadh, 11451, Saudi Arabia. lamjed.mansour@gmail.com.|Faculty of Sciences of Gabès, University of Gabès, Erriadh City, 6072, Zrig Gabès, Tunisia. lamjed.mansour@gmail.com.
authors.forename: Lamjed
authors.initials: L
authors.lastname: Mansour
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics*; D012529:Saudi Arabia / Q000453:epidemiology
chemical_list: D015236:HLA-C Antigens; D054340:Receptors, KIR
keywords: Genetic association; HLA ligands; Malignant diseases; Natural killer cells