Breast cancer: genetic risk or protection in Italian individuals.

Breast cancer (BC) is one of the most common and malignant disease among women and hormonal and environmental factors could be involved in the presentation of BC. There is also evidence that genetic factors may favour or interfere with the occurrence of BC. The innate immune system with natural killer receptors (KIR) recognizing class I HLA molecules and tumor surveillance with HLA class II antigens presenting of tumor peptides to T lymphocytes are involved in anti-tumor immune response. The aim of this study was to investigate the association between the KIR genes and HLA-C alleles in Italian patients with BC and matched controls (Ctrs). In addition, we analysed the potential relationship between HLA-DRB1 alleles and cancer. Our SSP results regarding KIR and HLA-C gene polymorphisms (43 BC pts and 39 Italian female controls) showed a higher incidence of KIR2DS1 gene in advanced carcinoma pts (stage III-IV) compared to stage I-II patients (66.7% vs 28.0% p=0.0156; 46.1% in Ctrs). In particular, the KIR2DS1/HLA-C2+ combination was predisposing to a more advanced cancer (III-IV 42.9% vs I-II 6.3%, p=0.0309). On the contrary, KIR2DS4ins alleles seemed to be protective towards more advanced stages (11.1% vs 35.9% in Ctrs, p=0.06). In addition, HLA-DRB1 sequencing of 114 breast cancer patients and 120 female donors revealed the association of DRB1*11:03 allele with an increased risk to develop BC (p=0.025, OR=3.5674) and a protective role of HLA-DRB1*16:01 towards the BC cancer onset (p=0.019, OR=0.2328). Our findings suggest a potential role of KIR activating receptors licensed by HLA-C ligands in BC tumoral progression and an effect of some MHC class II alleles in the etiopathogenesis, suggesting that in the development of breast cancer exists a disorder of immune regulation.