Genetic linkage analysis applied to unaffected women from families with breast cancer can discriminate high- from low-risk individuals.
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 non-mutation 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 MFD188, 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.
Porter
D E
DE
Medical Research Council Human Genetics Unit, Royal Infirmary, Edinburgh, UK.
Steel
C M
CM
Cohen
B B
BB
Wallace
M R
MR
Carothers
A
A
Chetty
U
U
Carter
D C
DC
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D005190:Family; D005260:Female; D016147:Genes, Tumor Suppressor; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D010375:Pedigree; D012307:Risk Factors
D005819:Genetic Markers