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A Genome wide linkage search for breast cancer susceptibility genes

Smith, Paula, McGuffog, Lesley, Easton, Douglas F., Mann, Graham J., Pupo, Gulietta M., Newman, Beth M., Chenevix-Trench, Georgia, Szabo, Csilla, Southey, Melissa, Renard, Helene, 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, & Stratton, Michael R. (2006) A Genome wide linkage search for breast cancer susceptibility genes. Genes, Chromosomes and Cancer, 45(7), pp. 646-655.

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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 1 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.

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ID Code: 10646
Item Type: Journal Article
Additional Information: For more information, please refer to the journal's website (see hypertext link) or contact the author.
DOI: 10.1002/gcc.20330
ISSN: 1098-2264
Subjects: Australian and New Zealand Standard Research Classification > MATHEMATICAL SCIENCES (010000) > PURE MATHEMATICS (010100) > Mathematical Logic Set Theory Lattices and Universal Algebra (010107)
Divisions: Current > Research Centres > Centre for Health Research
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 John Wiley & Sons
Deposited On: 09 Nov 2007
Last Modified: 29 Feb 2012 23:30

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