Genetic linkage analysis applied to unaffected women from families with breast cancer can discriminate high- from low-risk individuals

Abstract

Abstract Up to 20 per cent of cases of breast cancer diagnosed in women under the age of 45 years may be caused by an autosomal dominant gene. A present difficulty is differentiation of mutation carriers from nonmutation carriers in high-risk families. Genetic linkage analysis has been used to localize a susceptibility gene (BRCA1) on chromosome 17q12-21 between markers 42D6 and MFD 188, a region 5–10 million base pairs in length. Odds in favour of linkage to this region were greater than 100 000: 1 in 15 families with breast cancer. In eight families in which the probability of linkage was above 75 (range 79·2–99·9) per cent, 19 women were identified who were at high lifetime risk of breast cancer (range 80·6–87·2 per cent) and 37 whose risk was similar to that for the general population (range 9·8–16·4 per cent). Genetic risk prediction of this kind may enable high-risk screening clinic resources to be concentrated on those most likely to benefit.