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Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium

Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium
Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium
The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion ({alpha}) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603–9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result ({alpha} = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at {alpha} = 0.65 was –11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.
0027-8424
827-831
Thompson, Deborah
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Szabo, Csilla I.
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Mangion, Jon
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Oldenburg, Rogier A.
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Devilee, Peter
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Easton, Douglas F.
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Goldgar, David E.
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Thompson, Deborah
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Szabo, Csilla I.
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Mangion, Jon
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Oldenburg, Rogier A.
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Odefrey, Fabrice
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Kroeze-Jansema, Karin
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Teare, Dawn
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Rahman, Nazneen
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Mann, Graham
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Senie, Ruby
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Daly, Mary B.
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West, Dee
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Ostrander, Elaine
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Offit, Ken
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Nathanson, Katherine L.
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Sinilnikova, Olga M.
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Olàh, Edith
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Badzioch, Michael D.
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Vasen, Hans F.A.
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Phelan, Catherine M.
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Narod, Steven A.
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Lynch, Henry T.
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Ponder, Bruce A.J.
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Eeles, Ros A.
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Meijers-Heijboer, Hanne
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Stoppa-Lyonnet, Dominique
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Couch, Fergus J.
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Eccles, Diana M.
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Evans, D. Gareth
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Chang-Claude, Jenny
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Lenoir, Gilbert
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Weber, Barbara L.
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Devilee, Peter
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Easton, Douglas F.
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Goldgar, David E.
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Stratton, Michael R.
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Thompson, Deborah, Szabo, Csilla I., Mangion, Jon, Oldenburg, Rogier A., Odefrey, Fabrice, Seal, Sheila, Barfoot, Rita, Kroeze-Jansema, Karin, Teare, Dawn, Rahman, Nazneen, Renard, Hélène, Mann, Graham, Hopper, John L., Buys, Saundra S., Andrulis, Irene L., Senie, Ruby, Daly, Mary B., West, Dee, Ostrander, Elaine, Offit, Ken, Peretz, Tamar, Osorio, Ana, Benitez, J., Nathanson, Katherine L., Sinilnikova, Olga M., Olàh, Edith, Bignon, Yves-Jean, Ruiz, Pablo, Badzioch, Michael D., Vasen, Hans F.A., Futreal, Andrew P., Phelan, Catherine M., Narod, Steven A., Lynch, Henry T., Ponder, Bruce A.J., Eeles, Ros A., Meijers-Heijboer, Hanne, Stoppa-Lyonnet, Dominique, Couch, Fergus J., Eccles, Diana M., Evans, D. Gareth, Chang-Claude, Jenny, Lenoir, Gilbert, Weber, Barbara L., Devilee, Peter, Easton, Douglas F., Goldgar, David E. and Stratton, Michael R. (2002) Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium. Proceedings of the National Academy of Sciences, 99 (2), 827-831. (doi:10.1073/pnas.012584499).

Record type: Article

Abstract

The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion ({alpha}) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603–9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result ({alpha} = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at {alpha} = 0.65 was –11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.

Full text not available from this repository.

More information

Published date: 2002
Additional Information: PNAS
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 26637
URI: http://eprints.soton.ac.uk/id/eprint/26637
ISSN: 0027-8424
PURE UUID: 487ef48c-04ed-493f-88e8-9fa5835516d1

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Date deposited: 21 Apr 2006
Last modified: 15 Jul 2019 19:13

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Contributors

Author: Deborah Thompson
Author: Csilla I. Szabo
Author: Jon Mangion
Author: Rogier A. Oldenburg
Author: Fabrice Odefrey
Author: Sheila Seal
Author: Rita Barfoot
Author: Karin Kroeze-Jansema
Author: Dawn Teare
Author: Nazneen Rahman
Author: Hélène Renard
Author: Graham Mann
Author: John L. Hopper
Author: Saundra S. Buys
Author: Irene L. Andrulis
Author: Ruby Senie
Author: Mary B. Daly
Author: Dee West
Author: Elaine Ostrander
Author: Ken Offit
Author: Tamar Peretz
Author: Ana Osorio
Author: J. Benitez
Author: Katherine L. Nathanson
Author: Olga M. Sinilnikova
Author: Edith Olàh
Author: Yves-Jean Bignon
Author: Pablo Ruiz
Author: Michael D. Badzioch
Author: Hans F.A. Vasen
Author: Andrew P. Futreal
Author: Catherine M. Phelan
Author: Steven A. Narod
Author: Henry T. Lynch
Author: Bruce A.J. Ponder
Author: Ros A. Eeles
Author: Hanne Meijers-Heijboer
Author: Dominique Stoppa-Lyonnet
Author: Fergus J. Couch
Author: Diana M. Eccles
Author: D. Gareth Evans
Author: Jenny Chang-Claude
Author: Gilbert Lenoir
Author: Barbara L. Weber
Author: Peter Devilee
Author: Douglas F. Easton
Author: David E. Goldgar
Author: Michael R. Stratton

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