PMID- 27519478
OWN - NLM
STAT- MEDLINE
DCOM- 20171016
LR  - 20181113
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 14
IP  - 1
DP  - 2016 Aug 12
TI  - Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical 
      stage.
PG  - 239
LID - 10.1186/s12967-016-1001-y [doi]
LID - 239
AB  - BACKGROUND: 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 
      Fcgamma 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. METHODS: 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). RESULTS: 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)]. CONCLUSIONS: 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.
FAU - Canossi, Angelica
AU  - Canossi A
AD  - Laboratory of Tumor Immunology and Immunotherapy, CNR Institute of Translational 
      Pharmacology (IFT), Via Fosso del Cavaliere 100, 00133, L'Aquila, Rome, Italy.
FAU - Aureli, Anna
AU  - Aureli A
AD  - Laboratory of Tumor Immunology and Immunotherapy, CNR Institute of Translational 
      Pharmacology (IFT), Via Fosso del Cavaliere 100, 00133, L'Aquila, Rome, Italy.
FAU - Del Beato, Tiziana
AU  - Del Beato T
AD  - Laboratory of Tumor Immunology and Immunotherapy, CNR Institute of Translational 
      Pharmacology (IFT), Via Fosso del Cavaliere 100, 00133, L'Aquila, Rome, Italy.
FAU - Rossi, Piero
AU  - Rossi P
AD  - Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 
      Rome, Italy.
FAU - Franceschilli, Luana
AU  - Franceschilli L
AD  - Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 
      Rome, Italy.
FAU - De Sanctis, Flavio
AU  - De Sanctis F
AD  - Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 
      Rome, Italy.
FAU - Sileri, Pierpaolo
AU  - Sileri P
AD  - Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 
      Rome, Italy.
FAU - di Lorenzo, Nicola
AU  - di Lorenzo N
AD  - Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 
      Rome, Italy.
FAU - Buonomo, Oreste
AU  - Buonomo O
AD  - Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 
      Rome, Italy.
FAU - Lauro, Davide
AU  - Lauro D
AD  - Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
FAU - Venditti, Adriano
AU  - Venditti A
AD  - Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, 
      Italy.
FAU - Sconocchia, Giuseppe
AU  - Sconocchia G
AUID- ORCID: 0000-0003-3260-4856
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160812
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (FCGR3A protein, human)
RN  - 0 (HLA-C Antigens)
RN  - 0 (Ligands)
RN  - 0 (Receptors, IgG)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Case-Control Studies
MH  - Colorectal Neoplasms/*genetics/*pathology
MH  - Demography
MH  - Female
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-C Antigens/metabolism
MH  - Haplotypes/genetics
MH  - Humans
MH  - Italy
MH  - Ligands
MH  - Male
MH  - Neoplasm Staging
MH  - Receptors, IgG/*genetics
MH  - Receptors, KIR/*genetics
MH  - Risk Factors
PMC - PMC4983069
OTO - NOTNLM
OT  - CD16A
OT  - CRC
OT  - Colorectal carcinoma
OT  - FCGR3A genotypes
OT  - Genetic risk
OT  - KIR
OT  - NK
EDAT- 2016/08/16 06:00
MHDA- 2017/10/17 06:00
PMCR- 2016/08/12
CRDT- 2016/08/14 06:00
PHST- 2016/06/30 00:00 [received]
PHST- 2016/08/03 00:00 [accepted]
PHST- 2016/08/14 06:00 [entrez]
PHST- 2016/08/16 06:00 [pubmed]
PHST- 2017/10/17 06:00 [medline]
PHST- 2016/08/12 00:00 [pmc-release]
AID - 10.1186/s12967-016-1001-y [pii]
AID - 1001 [pii]
AID - 10.1186/s12967-016-1001-y [doi]
PST - epublish
SO  - J Transl Med. 2016 Aug 12;14(1):239. doi: 10.1186/s12967-016-1001-y.