A genome wide linkage search for breast cancer susceptibility genes

Paula Smith, Lesley McGuffog, Douglas F. Easton, Graham J. Mann, Gulietta M. Pupo, Beth Newman, Georgia Chenevix-Trench, Csilla Szabo, Melissa Southey, Hélène Renard, Fabrice Odefrey, Henry T. Lynch, Dominique Stoppa-Lyonnet, Fergus Couch, John L. Hopper, Graham G. Giles, Margaret R E McCredie, Saundra Buys, Irene Andrulis, Ruby Senie & 27 others David E. Goldgar, Rogier Oldenburg, Karin Kroeze-Jansema, Jaennelle Kraan, Hanne Meijers-Heijboer, Jan G M Klijn, Christi Van Asperen, Inge Van Leeuwen, Hans F A Vasen, Cees J. Cornelisse, Peter Devilee, Linda Baskcomb, Sheila Seal, Rita Barfoot, Jon Mangion, Anita Hall, Sarah Edkins, Elizabeth Rapley, Richard Wooster, Jenny Chang-Claude, Diana Eccles, D. Gareth Evans, P. Andrew Futreal, Katherine L. Nathanson, Barbara L. Weber, Nazneen Rahman, Michael R. Stratton

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)646-655
Number of pages10
JournalGenes Chromosomes and Cancer
Volume45
Issue number7
DOIs
StatePublished - Jul 2006

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Neoplasm Genes
Genome
Breast Neoplasms
Mutation
Chromosomes, Human, Pair 4
Chromosomes
Genes

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Genetics

Cite this

Smith, P., McGuffog, L., Easton, D. F., Mann, G. J., Pupo, G. M., Newman, B., ... Stratton, M. R. (2006). A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes and Cancer, 45(7), 646-655. https://doi.org/10.1002/gcc.20330

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; Chenevix-Trench, Georgia; Szabo, Csilla; Southey, Melissa; Renard, Hélène; Odefrey, Fabrice; Lynch, Henry T.; 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.

In: Genes Chromosomes and Cancer, Vol. 45, No. 7, 07.2006, p. 646-655.

Research output: Contribution to journalArticle

Smith, P, McGuffog, L, Easton, DF, Mann, GJ, Pupo, GM, Newman, B, Chenevix-Trench, G, Szabo, C, Southey, M, Renard, H, Odefrey, F, Lynch, HT, Stoppa-Lyonnet, D, Couch, F, Hopper, JL, Giles, GG, McCredie, MRE, Buys, S, Andrulis, I, Senie, R, Goldgar, DE, Oldenburg, R, Kroeze-Jansema, K, Kraan, J, Meijers-Heijboer, H, Klijn, JGM, Van Asperen, C, Van Leeuwen, I, Vasen, HFA, Cornelisse, CJ, Devilee, P, Baskcomb, L, Seal, S, Barfoot, R, Mangion, J, Hall, A, Edkins, S, Rapley, E, Wooster, R, Chang-Claude, J, Eccles, D, Evans, DG, Futreal, PA, Nathanson, KL, Weber, BL, Rahman, N & Stratton, MR 2006, 'A genome wide linkage search for breast cancer susceptibility genes', Genes Chromosomes and Cancer, vol. 45, no. 7, pp. 646-655. https://doi.org/10.1002/gcc.20330
Smith P, McGuffog L, Easton DF, Mann GJ, Pupo GM, Newman B et al. A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes and Cancer. 2006 Jul;45(7):646-655. https://doi.org/10.1002/gcc.20330
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 T. ; 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. / A genome wide linkage search for breast cancer susceptibility genes. In: Genes Chromosomes and Cancer. 2006 ; Vol. 45, No. 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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AU - Newman, Beth

AU - Chenevix-Trench, Georgia

AU - Szabo, Csilla

AU - Southey, Melissa

AU - Renard, Hélène

AU - Odefrey, Fabrice

AU - Lynch, Henry T.

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AU - Oldenburg, Rogier

AU - Kroeze-Jansema, Karin

AU - Kraan, Jaennelle

AU - Meijers-Heijboer, Hanne

AU - Klijn, Jan G M

AU - Van Asperen, Christi

AU - Van Leeuwen, Inge

AU - Vasen, Hans F A

AU - Cornelisse, Cees J.

AU - Devilee, Peter

AU - Baskcomb, Linda

AU - Seal, Sheila

AU - Barfoot, Rita

AU - Mangion, Jon

AU - Hall, Anita

AU - Edkins, Sarah

AU - Rapley, Elizabeth

AU - Wooster, Richard

AU - Chang-Claude, Jenny

AU - Eccles, Diana

AU - Evans, D. Gareth

AU - Futreal, P. Andrew

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