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Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers

Spurdle, Amanda B.; Marquart, Louise; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga; Wan, Fei; Chen, Xiaoqing; Beesley, Jonathan; Singer, Christian F. and Dressler, Anne-Catharine, et al. (2011) In Cancer Epidemiology Biomarkers & Prevention 20(5). p.1032-1038
Abstract
Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2... (More)
Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR. (Less)
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Single Nucleotide, Polymorphism, Humans, Heterozygote, Germ-Line Mutation, Genotype, Genetic Predisposition to Disease, Female, Cohort Studies, Breast Neoplasms, BRCA1 Protein, BRCA2 Protein, Prognosis, Risk Factors, Tumor Markers, Biological, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases
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Cancer Epidemiology Biomarkers & Prevention
volume
20
issue
5
pages
1032 - 1038
publisher
American Association for Cancer Research
external identifiers
  • wos:000290251000037
  • scopus:79955775590
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-10-0909
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English
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e8559f4e-10ad-47dd-9713-d600c69245bc (old id 1987946)
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http://www.ncbi.nlm.nih.gov/pubmed/21393566
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2011-07-01 09:17:11
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2017-01-01 06:21:09
@article{e8559f4e-10ad-47dd-9713-d600c69245bc,
  abstract     = {Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR.},
  author       = {Spurdle, Amanda B. and Marquart, Louise and McGuffog, Lesley and Healey, Sue and Sinilnikova, Olga and Wan, Fei and Chen, Xiaoqing and Beesley, Jonathan and Singer, Christian F. and Dressler, Anne-Catharine and Gschwantler-Kaulich, Daphne and Blum, Joanne L. and Tung, Nadine and Weitzel, Jeff and Lynch, Henry and Garber, Judy and Easton, Douglas F. and Peock, Susan and Cook, Margaret and Oliver, Clare T. and Frost, Debra and Conroy, Don and Evans, D. Gareth and Lalloo, Fiona and Eeles, Ros and Izatt, Louise and Davidson, Rosemarie and Chu, Carol and Eccles, Diana and Selkirk, Christina G. and Daly, Mary and Isaacs, Claudine and Stoppa-Lyonnet, Dominique and Sinilnikova, Olga M. and Buecher, Bruno and Belotti, Muriel and Mazoyer, Sylvie and Barjhoux, Laure and Verny-Pierre, Carole and Lasset, Christine and Dreyfus, Helene and Pujol, Pascal and Collonge-Rame, Marie-Agnes and Rookus, Matti A. and Verhoef, Senno and Kriege, Mieke and Hoogerbrugge, Nicoline and Ausems, Margreet G. E. M. and van Os, Theo A. and Wijnen, Juul and Devilee, Peter and Meijers-Heijboer, Hanne E. J. and Blok, Marinus J. and Heikkinen, Tuomas and Nevanlinna, Heli and Jakubowska, Anna and Lubinski, Jan and Huzarski, Tomasz and Byrski, Tomasz and Durocher, Francine and Couch, Fergus J. and Lindor, Noralane M. and Wang, Xianshu and Thomassen, Mads and Domchek, Susan and Nathanson, Kate and Caligo, M. A. and Jernström, Helena and Liljegren, Annelie and Ehrencrona, Hans and Karlsson, Per and Ganz, Patricia A. and Olopade, Olufunmilayo I. and Tomlinson, Gail and Neuhausen, Susan and Antoniou, Antonis C. and Chenevix-Trench, Georgia and Rebbeck, Timothy R.},
  issn         = {1538-7755},
  keyword      = {Single Nucleotide,Polymorphism,Humans,Heterozygote,Germ-Line Mutation,Genotype,Genetic Predisposition to Disease,Female,Cohort Studies,Breast Neoplasms,BRCA1 Protein,BRCA2 Protein,Prognosis,Risk Factors,Tumor Markers,Biological,Tumor Suppressor Proteins,Ubiquitin-Protein Ligases},
  language     = {eng},
  number       = {5},
  pages        = {1032--1038},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-10-0909},
  volume       = {20},
  year         = {2011},
}