Single Nucleotide Polymorphism in the Interleukin 12 B Gene is Associated with Risk for Breast Cancer Development

Breast cancer is the most common malignancy in women, who have over 100-fold higher risk of developing disease than men. Despite the progress in treatment over the past years and relatively good overall survival at present (about 80% have an estimated 5-year survival rate), the disease has still caused over 450,000 deaths worldwide per year in the last decade. Recent novel therapies involve various cytokine treatments that promote anti-cancer-specific adaptive immunity. However, success of therapies might be greatly improved provided all risk factors were known. Cancer has a multi-factorial genetic susceptibility. The immune system can contribute to genetic risk to cancer; first, innate immunity can provide stimulation of cell growth by inflammation, a well-known tumour promotion factor, and second, adaptive immunity can detect and eliminate cancer cells according to the immunosurveillance hypothesis [1]. An increased former capacity or a weakness in the latter ability would increase susceptibility to cancer. Evidence that adaptive immunity has a role in cancer development comes from experiments in various animal models [2–9] and from data showing an increased incidence of cancers in humans with immunodeficiencies [10] or after receiving post-transplantation immunosuppression therapy [11, 12]. In line with this, CD4 T cell and CD1a dendritic cell populations in axillary lymph nodes were highly correlated predictors of disease-free survival in patients with breast cancer [13]. The IL-12 cytokine is important for adaptive immunity with a principal role in the defence against intracellular micro-organisms [14, 15]. It is a 70-kDa heterodimeric protein (IL-12 p70) composed of p35 *Molecular Genetics Laboratory, Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway; School of Medicine, University of Oslo, Oslo, Norway; School of Medicine, University of Zagreb, Zagreb, Croatia; §Department of Medical Oncology, Division of Oncology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia; –Division of Molecular Medicine, Ru der Bošković Institute, Zagreb, Croatia; and **Clinical Institute for Transfusion Medicine, Universal Hospital Center Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia