title: The Relationship Between Killer Cell Immunoglobulin-Like Receptors and HLA-C Polymorphisms in Colorectal Cancer in a Saudi Population.
abstract: OBJECTIVE
  We performed an association study to evaluate the contribution of 16 killer cell immunoglobulin-like receptor (KIR) genotype polymorphisms and the HLA-C1 and -C2 ligands in the development of colorectal cancer (CRC) in Saudi Arabian patients.
  
  
  METHODS
  A total of 52 patients with different stages of malignant CRC as well as 70 healthy Saudi controls were enrolled at the King Khalid University Hospital.
  
  
  RESULTS
  Our results showed that the frequency of the activating mutations KIR2DS1, 2DS2, 2DS3, 2DS5, and 3DS1 was significantly higher in CRC patients compared to controls. The 3DS1 gene contributed to the highest risk of CRC (odds ratio [OR] = 16.25, p < 0.0001), followed by 2DS1 (OR = 8.6; p < 0.0001). The distributions of HLA-C1 and -C2 ligands were not significantly different between patients and controls. Analyses of different combinations of KIR genes with their HLA-C1 and -C2 ligands show that the frequency of 2DL3 in the presence of its ligand, the allotype C1, was significantly more prevalent in patients compared to controls. In addition, 2DL2 and 2DL3 that were aggregated in combination with the ligand, HLA-C1, were found to be more highly associated mainly with the homozygote HLA-C1/C1 (p = 0.03; OR = 2.6). The activating mutations 2DS1 and 2DS2 when combined with their respective ligands, HLA-C2 and -C1, showed highly significant associations with CRC development.
  
  
  CONCLUSIONS
  This study supports a key role for KIR gene mutations in the development of CRC, especially in association with their ligands.
authors.affiliation: 1 Department of Zoology, College of Science, King Saud University , Riyadh, Saudi Arabia .
authors.forename: Suliman Y
authors.initials: SY
authors.lastname: Al Omar
authors.affiliation: 1 Department of Zoology, College of Science, King Saud University , Riyadh, Saudi Arabia .
authors.forename: Lamjed
authors.initials: L
authors.lastname: Mansour
authors.affiliation: 2 Central Laboratory College of Science, King Saud University , Riyadh, Saudi Arabia .
authors.forename: Javid Ahmed
authors.initials: JA
authors.lastname: Dar
authors.affiliation: 1 Department of Zoology, College of Science, King Saud University , Riyadh, Saudi Arabia .
authors.forename: Saleh
authors.initials: S
authors.lastname: Alwasel
authors.affiliation: 1 Department of Zoology, College of Science, King Saud University , Riyadh, Saudi Arabia .
authors.forename: Afrah
authors.initials: A
authors.lastname: Alkhuriji
authors.affiliation: 3 Department of Pathology, King Saud University , Riyadh, Saudi Arabia .
authors.forename: Maha
authors.initials: M
authors.lastname: Arafah
authors.affiliation: 4 Department of Surgery, Colorectal Research Center, King Saud University , Riyadh, Saudi Arabia .
authors.forename: Omar
authors.initials: O
authors.lastname: Al Obeed
authors.affiliation: 5 Department of Clinical Infection, Microbiology and Immunology, Faculty of Health and Life Sciences, Institute of Global Health, University of Liverpool , Liverpool, United Kingdom .
authors.forename: Stephen
authors.initials: S
authors.lastname: Christmas
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D054340:Receptors, KIR / Q000235:genetics*; D012529:Saudi Arabia
chemical_list: D015236:HLA-C Antigens; D007136:Immunoglobulins; D054340:Receptors, KIR