title: Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage.
abstract: NK cell cytotoxicity is regulated by the types of the interaction between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands on target cells and the different binding affinity of the Fcγ receptor IIIA (CD16A) for IgG-coated tumor cells. Thus, it is conceivable that KIR and CD16A gene contents may contribute to the function of NK cells by modulating an immune response in the colorectal carcinoma (CRC) microenvironment. This hypothesis is supported by recent evidence suggesting that NK cells improve the clinical course of CRC patients by enhancing the anti-CRC effect of CD8 + T cells. This information provides the rationale to test the hypothesis whether the independent KIR segregation and specificity, as well as CD16A gene polymorphisms, have an impact on CRC.
  
  
  
  Using polymerase chain reaction-sequence-specific primers (PCR-SSP) and sequence-based typing (SBT), we investigated KIR/HLA-C complex and CD16A (48H/R/L,158V/F) gene polymorphisms in 52 CRC patients and 61 local healthy controls (LCTRs).
  
  
  
  The allele frequency (AF) of at least five activating KIR (aKIRs) of the B haplotype (p = 0.036, OR 0.204), KIR2DL2 (p = 0.047, OR 0.2616), and KIR2DS2 genes (5.8 vs LCTR 13.8 % and vs. Fasano's CTR 16.3 %, p = 0.05, OR 0.3145), in the absence of their cognate HLA-C1 ligands, were significantly associated with a reduced genetic risk of CRC. In contrast, CD16A-48H polymorphism was positively associated with an increased genetic risk of CRC (p = 0.05, OR 2.761). The latter was also found to be correlated with advanced stages of disease [III and IV (p = 0.03, OR 3.625)].
  
  
  
  Our data suggest that the analysis of aKIRs and KIR2DL2 gene and CD16A-48H may be of interest for the identification of individuals at reduced and increased genetic risk of CRC, respectively.
authors: Laboratory of Tumor Immunology and Immunotherapy, CNR Institute of Translational Pharmacology (IFT), Via Fosso del Cavaliere 100, 00133, L'Aquila, Rome, Italy.
authors: Angelica
authors: A
authors: Canossi
authors: Laboratory of Tumor Immunology and Immunotherapy, CNR Institute of Translational Pharmacology (IFT), Via Fosso del Cavaliere 100, 00133, L'Aquila, Rome, Italy.
authors: Anna
authors: A
authors: Aureli
authors: Laboratory of Tumor Immunology and Immunotherapy, CNR Institute of Translational Pharmacology (IFT), Via Fosso del Cavaliere 100, 00133, L'Aquila, Rome, Italy.
authors: Tiziana
authors: T
authors: Del Beato
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Piero
authors: P
authors: Rossi
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Luana
authors: L
authors: Franceschilli
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Flavio
authors: F
authors: De Sanctis
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Pierpaolo
authors: P
authors: Sileri
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Nicola
authors: N
authors: di Lorenzo
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Oreste
authors: O
authors: Buonomo
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors: Davide
authors: D
authors: Lauro
authors: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
authors: Adriano
authors: A
authors: Venditti
authors: Laboratory of Tumor Immunology and Immunotherapy, CNR Institute of Translational Pharmacology (IFT), Via Fosso del Cavaliere 100, 00133, L'Aquila, Rome, Italy. giuseppe.sconocchia@cnr.it.
authors: Giuseppe
authors: 0000-0003-3260-4856
authors: G
authors: Sconocchia
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D003710:Demography; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015236:HLA-C Antigens / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy; D008024:Ligands; D008297:Male; D009367:Neoplasm Staging; D017452:Receptors, IgG / Q000235:genetics*; D054340:Receptors, KIR / Q000235:genetics*; D012307:Risk Factors
chemical_list: C496124:FCGR3A protein, human; D015236:HLA-C Antigens; D008024:Ligands; D017452:Receptors, IgG; D054340:Receptors, KIR
keywords: CD16A; CRC; Colorectal carcinoma; FCGR3A genotypes; Genetic risk; KIR; NK