Genetic insights into familial cancers – update and recent discoveries

While the vast majority of cancers are believed to occur sporadically, most forms of cancer, both adult and paediatric, have a hereditary equivalent. In the case of adult malignancies, these include hereditary breast and ovarian cancer and syndromes such as the multiple endocrine neoplasias types 1 and 2 characterised by specific tumours of the endocrine gland system. In the case of paediatric malignancies, these include syndromes such as retinoblastoma and Wilms tumour. In a little over a single decade, we have seen a tremendous increase in the knowledge of the primary genetic basis of many of the familial cancer syndromes. The majority of familial syndromes are inherited as autosomal dominant traits including hereditary colon cancer and familial malignant melanoma, however, the genetics behind autosomal recessive disorders such as Bloom syndrome and Fanconi anaemia are also being elucidated. A third mode of inheritance less well understood in the setting of familial cancer is that of imprinting recently observed in a subset of families with inherited paraganglioma. In this review, we discuss 31 genes inherited in an autosomal dominant manner associated with 20 familial cancer syndromes. Genes inherited in an autosomal recessive manner linked to familial cancer syndromes are also discussed. The identification of genes associated with familial cancer syndromes has in some families enabled a ‘molecular diagnosis’ that complements clinical assessment and allows directed cancer surveillance for those individuals determined to be at-risk of disease.