INFLUENCE OF KIR/HLA-C AND FCGR3A GENE POLYMORPHISMS IN ETIOPATHOGENESIS AND PROGRESSION OF COLORECTAL CARCINOMAS

Antitumor cytotoxicity of NK and T cells is regulated by interaction between killer immunoglobulin-like receptors (KIR) and MHCclass I ligands on target cells and by different binding affinity of Fc?R receptors with IgG-coated tumor cells. Using PCR-SSPand SBT assays, we investigated possible association of KIR and FCGR3A (158 V/F) gene polymorphisms and the incidence ofcolorectal cancer (CRC) in 52 patients and Italian controls (CTRS), in order to provide insights into the role of NK cells in thecontrol of tumor growth. Comparing the frequency of KIR genes between CRC patients (pts) in different stages of disease (I-II andIII-IV) and Italian controls (CTRS), we noted a significantly higher incidence of the KIR2DL5B gene in pts (CRC 50.0% vs CTRS28.1% p=0.004), and particularly in early stages of disease (58.1% vs 28.1% p=0.0016) and rectal cancer group (57.9% vs 28.1%p=0.016). Combining KIR genes and their ligands, we observed: a) a protective role of the inhibitory KIR2DL2 and KIR2DL3genes taken together (15.4% vs 34.8%, p=0.0054) and/or the activating KIR2DS2 (5.7% vs 16.3, p=0.05) in the absence ofits ligand HLA-C1; b) a predisposing effect of KIR2DS2 with its C1 ligand (57.7% vs 41.5% p=0.033); c) a protective roleof the FCGR3A-158Val in KIR2DL5B + pts towards colorectal cancer progression (75.0% vs 25.0%, p=0.0024). These datasuggest a prevalence of inhibitory over activating signals in tumor dissemination and/or a hypothetical inflammatory involvement ofKIR2DS2, linked to the presence of HLA ligands specific for their homologous inhibitory receptors KIR2DL2/3.