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. A family history of breast cancer is one of the most consistent risk factors of the neoplasm, particularly in women who have multiple relatives with bilateral premenopausal disease. Recent data have identified at least five genes predisposing to inherited breast cancer. Clinically, the most important is the BRCA1 gene, located on chromosome 17q. Corresponding figures for breast and ovarian cancers associated with inherited BRCA2 mutations may be lower.