Germline mutations of the brca1 gene in breast and ovarian cancer families provide evidence for a genotype–phenotype correlation

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. Access through your institution Buy or subscribe This is a preview of subscription

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contributed equally to the study. AUTHORS AND AFFILIATIONS * CRC Human Cancer Genetics Research Group, Addenbrooke's Hospital, Box 238, Hills Road, Cambridge, CB2 2QQ, UK Simon A.

Gayther, Sylvie Mazoyer, Paul A. Russell, Patricia A. Harrington, Mathias Chiano, Elizabeth J. van Rensburg, Alison M. Dunning & Bruce A.J. Ponder * Section of Molecular Carcinogenesis,

Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK William Warren, Sheila Seal, Rifat Hamoudi & Michael R. Stratton * MRC Biostatistics

Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge, CB2 2SR, UK Mathias Chiano & David Clayton * Department of Human Genetics, University of Pretoria, P.O.

Box 2034, Pretoria, 0001, South Africa Elizabeth J. van Rensburg * Cancer Prevention Programme, 1300 University Avenue, 7C, Madison, Wisconsin, 53706, USA Richard Love * Regional Genetics

Service, St. Mary's Hospital Manchester, Whitworth Park, Manchester, M13 OJH, UK Gareth Evans * Department of Community Medicine, Institute of Public Health, University Forvie Site,

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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 Download citation *

Received: 31 July 1995 * Accepted: 06 October 1995 * Issue Date: 01 December 1995 * DOI: https://doi.org/10.1038/ng1295-428 SHARE THIS ARTICLE Anyone you share the following link with will

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