Genes implicated in hereditary breast cancer syndromes

The medical histories of breast cancer-prone families have been described f or over a century. The pattern of breast cancer occurrences in these famili es is most consistent with an autosomal dominant mode of inheritance. The l ocation of a gene that could explain the pattern of transmission of the bre ast cancer trait in families averaging early (pre-menopausal) onset of brea st cancer was reported in 1990. Since then, two genes have been identified: BRCA1 and BRCA2. Germ-line mutations in these two genes confer susceptibil ity to breast (female and male) and ovarian cancer, and account for a signi ficant proportion of hereditary breast cancer in two cancer syndromes: site -specific breast cancer and the breast-ovarian cancer syndrome. Other hered itary syndromes that feature breast cancer are Li-Fraumeni syndrome, Cowden disease, and ataxia telangiectasia, whose carriers have been shown to harb or germ-line mutations in TP53, PTEN, and ATM, respectively. There may be o ther genetic factors that contribute to hereditary breast cancer, since not all families with multiple cases of breast cancer harbor germ-line BRCA1 o r BRCA2 mutations. Host factors (such as lifestyle choices) and other genes may modulate risk of breast cancer in mutation carriers. Semin, Surg. Onco l, 18:281-286, 2000, (C) 2000 Wiley-Liss, Inc.