Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Canossi, Angelica; Aureli, Anna; Beato, Tiziana; Rossi, Piero; Franceschilli, Luana; Sanctis, Flavio; Sileri, Pierpaolo; Lorenzo, Nicola; Buonomo, Oreste; Lauro, Davide; Venditti, Adriano; Sconocchia, Giuseppe
• Is Part Of: Journal of translational medicine. Volume 14:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: NK -- KIR -- CD16A -- FCGR3A genotypes -- Colorectal carcinoma -- CRC -- Genetic risk; Medicine, Experimental -- Periodicals; Human experimentation in medicine -- Periodicals; Therapeutics -- Periodicals; 615.50724
• DOI: 10.1186/s12967-016-1001-y
• Languages: English
• ISSNs: 1479-5876

Abstract

Abstract 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 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. 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.