Genetics and cancer.

In the past year we have witnessed significant progress in understanding the molecular basis of cancerogenesis and in identifying the genetic determinants of susceptibility to cancer. In particular, the finding that the same tumor suppressor genes play a pathogenic role in both the inherited and the sporadic forms of some childhood tumors has suggested that this gene class may also be involved in adult tumors derived from inherited familial cancer syndromes. The identification of the gene defect underlying the Li-Fraumeni syndrome, a germline mutation of the tumor suppressor gene p53, has fully confirmed that suggestion. Three other genes associated with the inherited cancer syndromes neurofibromatosis type I (NF-1) and familial adenomatous polyposis have been cloned and partially characterized. In addition to these genes, which have a relatively high penetrance and contribute directly to tumorigenesis, other genes that lead to cancer as a secondary effect seem to act in determining an individual's overall cancer risk. The latter genes are most likely related to defective processes of DNA repair or to regulation of carcinogen metabolism. In this context the analysis of models of murine strains with different genetic susceptibility to cancer of various organs may be a useful tool for unveiling the genetic basis for cancer susceptibility in individuals.