The RB1 gene is a tumor suppressor. Loss or inactivation of both alleles of the gene abolishes its tumor suppressor function and leads to tumor development. In hereditary retinoblastoma, one abnormal allele has been inherited from a parent. Although inherited mutations in the RB1 gene are rare, somatic mutations in the gene are active in the genesis of many forms of cancer, including carcinoma of the breast, lung, and other sites. The RB1 protein interacts with the transcription factors and cyclins that regulate progression through the cell cycle.
Neoplasia is the primary manifestation of some cancer genes, such as the retinoblastoma gene.
Carriers of these genes can often be identified by a family history of the same cancer in multiple relatives affected at unusually early ages. In other genetic disorders, such as neurofibromatosis, cancer is a less common manifestation of the underlying genetic disease. The finding of a predisposing genetic disorder should alert the physician to the possibility of early diagnosis of associated cancers through periodic surveillance. Colorectal cancer tends to develop within certain families. The APC tumor suppressor gene was isolated in 1991 and shown to be the inherited mutation in all polyposis families.