Abstract
Mutations in the BRCA1 gene, discovered in 1994, are associated with an 80–90% lifetime risk of breast cancer. We have analysed 60 families with a history of breast and/or ovarian cancer for germline mutations in BRCA1. Twenty–two different mutations were detected in 32 families (53%), of which 14 are previously unreported. We observed a significant correlation between the location of the mutation in the gene and the ratio of breast to ovarian cancer incidence within each family. Our data suggest a transition in risk such that mutations in the 3′ third of the gene are associated with a lower proportion of ovarian cancer. Haplotype analysis supports previous data which suggest some BRCA1 mutation carriers have common ancestors; however, we have found at least two examples where recurrent mutations appear to have arisen independently.
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Gayther, S., Warren, W., Mazoyer, S. et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype–phenotype correlation. Nat Genet 11, 428–433 (1995). https://doi.org/10.1038/ng1295-428
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DOI: https://doi.org/10.1038/ng1295-428
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