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A genome wide linkage search for breast cancer susceptibility genes

A genome wide linkage search for breast cancer susceptibility genes
A genome wide linkage search for breast cancer susceptibility genes
Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome-wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over I were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2. (c) 2006 Wiley-Liss, Inc
brca1, susceptibility, breast cancer, mutation, locus, penetrance, breast, mutations, brca2, families, genes, familial breast, model, region, chek2-asterisk-1100delc, gene, brca2 mutations, chromosome 8p12-p22, risks, age, disease, breast-cancer, candidate, ovarian-cancer, cancer susceptibility, prevalence, cancer
1045-2257
646-655
Smith, Paula
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McGuffog, Lesley
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Easton, Douglas F.
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Mann, Graham J.
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Pupo, Gulietta M.
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Newman, Beth
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Chenevix-Trench, Georgia
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Szabo, Csilla
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Southey, Melissa
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Renard, Hélène
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Odefrey, Fabrice
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Lynch, Henry
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Stoppa-Lyonnet, Dominique
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Couch, Fergus
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Hopper, John L.
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Giles, Graham G.
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McCredie, Margaret R.E.
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Andrulis, Irene
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Senie, Ruby
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Goldgar, David E.
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Oldenburg, Rogier
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Kroeze-Jansema, Karin
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Kraan, Jaennelle
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Meijers-Heijboer, Hanne
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Klijn, Jan G.M.
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van Asperen, Christi
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van Leeuwen, Inge
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Vasen, Hans F.A.
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Cornelisse, Cees J.
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Devilee, Peter
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Baskcomb, Linda
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Seal, Sheila
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Barfoot, Rita
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Mangion, Jon
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Hall, Anita
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Edkins, Sarah
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Rapley, Elizabeth
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Wooster, Richard
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Chang-Claude, Jenny
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Eccles, Diana
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Evans, D. Gareth
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Futreal, P. Andrew
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Nathanson, Katherine L.
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Weber, Barbara L.
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Rahman, Nazneen
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Stratton, Michael R.
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Smith, Paula
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McGuffog, Lesley
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Easton, Douglas F.
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Mann, Graham J.
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Pupo, Gulietta M.
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Newman, Beth
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Chenevix-Trench, Georgia
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Szabo, Csilla
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Southey, Melissa
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Renard, Hélène
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Odefrey, Fabrice
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Lynch, Henry
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Stoppa-Lyonnet, Dominique
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Couch, Fergus
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Hopper, John L.
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Giles, Graham G.
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McCredie, Margaret R.E.
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Buys, Saundra
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Andrulis, Irene
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Senie, Ruby
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Goldgar, David E.
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Oldenburg, Rogier
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Kroeze-Jansema, Karin
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Kraan, Jaennelle
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Meijers-Heijboer, Hanne
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Klijn, Jan G.M.
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van Asperen, Christi
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van Leeuwen, Inge
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Vasen, Hans F.A.
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Cornelisse, Cees J.
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Devilee, Peter
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Baskcomb, Linda
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Seal, Sheila
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Barfoot, Rita
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Mangion, Jon
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Hall, Anita
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Edkins, Sarah
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Rapley, Elizabeth
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Wooster, Richard
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Chang-Claude, Jenny
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Eccles, Diana
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Evans, D. Gareth
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Futreal, P. Andrew
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Nathanson, Katherine L.
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Weber, Barbara L.
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Rahman, Nazneen
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Stratton, Michael R.
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Smith, Paula, McGuffog, Lesley, Easton, Douglas F., Mann, Graham J., Pupo, Gulietta M., Newman, Beth, Chenevix-Trench, Georgia, Szabo, Csilla, Southey, Melissa, Renard, Hélène, Odefrey, Fabrice, Lynch, Henry, Stoppa-Lyonnet, Dominique, Couch, Fergus, Hopper, John L., Giles, Graham G., McCredie, Margaret R.E., Buys, Saundra, Andrulis, Irene, Senie, Ruby, Goldgar, David E., Oldenburg, Rogier, Kroeze-Jansema, Karin, Kraan, Jaennelle, Meijers-Heijboer, Hanne, Klijn, Jan G.M., van Asperen, Christi, van Leeuwen, Inge, Vasen, Hans F.A., Cornelisse, Cees J., Devilee, Peter, Baskcomb, Linda, Seal, Sheila, Barfoot, Rita, Mangion, Jon, Hall, Anita, Edkins, Sarah, Rapley, Elizabeth, Wooster, Richard, Chang-Claude, Jenny, Eccles, Diana, Evans, D. Gareth, Futreal, P. Andrew, Nathanson, Katherine L., Weber, Barbara L., Rahman, Nazneen and Stratton, Michael R. (2006) A genome wide linkage search for breast cancer susceptibility genes. Genes, Chromosomes and Cancer, 45 (7), 646-655. (doi:10.1002/gcc.20330).

Record type: Article

Abstract

Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome-wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over I were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2. (c) 2006 Wiley-Liss, Inc

Full text not available from this repository.

More information

Published date: 30 March 2006
Keywords: brca1, susceptibility, breast cancer, mutation, locus, penetrance, breast, mutations, brca2, families, genes, familial breast, model, region, chek2-asterisk-1100delc, gene, brca2 mutations, chromosome 8p12-p22, risks, age, disease, breast-cancer, candidate, ovarian-cancer, cancer susceptibility, prevalence, cancer

Identifiers

Local EPrints ID: 62931
URI: http://eprints.soton.ac.uk/id/eprint/62931
ISSN: 1045-2257
PURE UUID: 7f745866-11a2-4a02-bd95-6fb187c88bee

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Date deposited: 04 Sep 2008
Last modified: 13 Mar 2019 20:26

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Contributors

Author: Paula Smith
Author: Lesley McGuffog
Author: Douglas F. Easton
Author: Graham J. Mann
Author: Gulietta M. Pupo
Author: Beth Newman
Author: Georgia Chenevix-Trench
Author: Csilla Szabo
Author: Melissa Southey
Author: Hélène Renard
Author: Fabrice Odefrey
Author: Henry Lynch
Author: Dominique Stoppa-Lyonnet
Author: Fergus Couch
Author: John L. Hopper
Author: Graham G. Giles
Author: Margaret R.E. McCredie
Author: Saundra Buys
Author: Irene Andrulis
Author: Ruby Senie
Author: David E. Goldgar
Author: Rogier Oldenburg
Author: Karin Kroeze-Jansema
Author: Jaennelle Kraan
Author: Hanne Meijers-Heijboer
Author: Jan G.M. Klijn
Author: Christi van Asperen
Author: Inge van Leeuwen
Author: Hans F.A. Vasen
Author: Cees J. Cornelisse
Author: Peter Devilee
Author: Linda Baskcomb
Author: Sheila Seal
Author: Rita Barfoot
Author: Jon Mangion
Author: Anita Hall
Author: Sarah Edkins
Author: Elizabeth Rapley
Author: Richard Wooster
Author: Jenny Chang-Claude
Author: Diana Eccles
Author: D. Gareth Evans
Author: P. Andrew Futreal
Author: Katherine L. Nathanson
Author: Barbara L. Weber
Author: Nazneen Rahman
Author: Michael R. Stratton

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