The A-T gene does not make a major contribution to familial breast cancer

Abstract

Breast cancer is known to have a strong familial component, consistent in some families with autosomal dominant inheritance. It has been estimated that approximately 5% of breast cancers may be the result of a highly penetrant autosomal dominant gene (Claus et al., 1991). Such individuals tend to develop breast cancer at an early age, have a high prevalence of bilaterality and are at an elevated risk of other neoplasms (Lynch and Hirayam, 1989). Recently the location of a gene predisposing to both breast and ovarian cancer on chromosome 17q (BRCA1) has been established by genetic linkage analysis (Hall et al., 1990). In an analysis of 214 breast cancer families worldwide, the proportion of families linked to this locus was estimated to be 100% for breast-ovarian cancer families and 45% for families with multiple cases of breast cancer only (Easton et al., 1993). Among breast cancer families without cases of ovarian cancer, a small minority have features of the Li-Fraumeni syndrome (sarcomas in children associated with early onset breast cancer in female relatives) and a proportion of these families are associated with germline mutations in the p53 gene on chromosome 17p (Malkin et al., 1990).