Impact of HLA Class I Antigen, Killer Ig-like Receptor and FCGR3A Genotypes in Breast Cancer Susceptibility and Tumor stage

Abstract The identification of clinical pathological role of genes regulating NK cell function, including HLA, KIR and FCGR3A, in breast cancer (BC) may be a challenge. The objective of this study was to determine whether these genes have an impact on the BC susceptibility and progression. In this study, 47 BC Italian patientswere genotyped by PCR-SSP typing (KIR) and PCR-SBT method (HLA-C and FCGR3A). HLA-C allele analysis showed that the HLA-C*07:02:01 (p = 0.04, OR = 4.867) and HLA-C*04:01:01 alleles (p = 0.04 OR = 2.364) were predisposing to tumor progression, and instead the HLA-C*05:01:01 allele was protective against disease (p = 0.019 OR = 0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (p = 0.022) and an increased coexistence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to early stages (p = 0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p = 0.012 OR = 5.020) or with lymph node involvement (p = 0.008 OR = 6.375). We identified different combinations of the FCGR3A-48/158 haplotypes and KIR genes in BC patients compared to controls. Our study provides evidence that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients.