Hereditary Cancers and Genetics

The study of hereditary syndromes is fundamentally based on the finding and identification of susceptibility genes underlying the pathology. Although hereditary tumors account for only a small fraction of all the tumors, the knowledge of underlying genetics changed the clinical management of affected patients and their families, also providing important information on the molecular mechanisms involved in the development of sporadic tumors. In the subjects who inherit a germline mutation, all the cells of the organism are carriers of that mutation, predisposing such subject to develop neoplasm more easily and earlier compared to the general population. The identification of individuals with a hereditary risk of cancer is based on an accurate reconstruction of their personal and family clinical history. Oncogenes and tumor suppressor genes are generally considered genes whose alterations are involved in the tumor onset and progression, promoting an abnormal cell growth and division. Hereditary predisposition syndromes are associated with germline mutations which determine the activation of oncogenes or inactivation of tumor suppressor genes. Tumor suppressor genes responsible for the heredofamilial cancer syndromes can be schematically divided into three main categories: gatekeepers, caretakers, and landscapers. Gatekeeper genes act by directly controlling cell growth, thus inhibiting proliferation, and leading to the apoptosis. Caretakers are responsible for maintaining genomic stability, by reducing the mutation rates of different genes involved in DNA repair, including gatekeepers and oncogenes.