[Hereditary neoplastic diseases (genetic predisposition and cancer syndromes)]

After one decade of molecular genetic studies, little doubt remains that cancer is a genetic disease. While mutations in somatic cells may cause cancer, they don't carry forward to the next generation. In fact, most cancers arise in this way. In some individuals mutations in cancer related genes may be present at the constitutional level, inherited from one of the parents. An individual who carries a mutant allele of an inherited cancer gene has a variable risk of cancer that is influenced by other genetic and non-genetic factors (such as other cellular genes, dietary, lifestyle, and environmental factors). Collectively, the syndromes affect about 1% of cancer patients. During the past decade about 25 different cancer susceptibility genes have been reported to be linked to the known hereditary cancer syndromes. Over the period of the last three to five years, studies of the specific mutations responsible for these syndromes and the cellular signaling pathways disrupted by the mutant proteins have begun to provide unprecedented insights into the molecular origin and pathogenesis of inherited and sporadic forms of cancer. This article reviews the cancer susceptibility genes and cancer syndromes, particularly those associated with common malignancies (breast, prostate and colorectal carcinomas). Results of the mutation analysis in BRCA1 and BRCA2 genes of Hungarian breast/ovarian cancer families will be briefly discussed. These data indicate a strong founder effect for some mutations of BRCA1 gene in Hungary. As a results of recent publicity of discoveries of molecular genetics--particularly those related to common malignancies--due to publicity in the scientific and the lay press awareness and demand for predictive DNA tests have dramatically increased worldwide over the past 3 years. The author, as a member of the Breast Cancer Linkage Consortium, shares the consensus view that genetic testing and genetic counseling for cancer risk together with surveillance and management should for the present be offered only through specialist clinical genetic departments as part of a research evaluation.