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

Research output: Contribution to journalArticle


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.


  • Amanda B. Spurdle
  • Louise Marquart
  • Lesley McGuffog
  • Sue Healey
  • Olga Sinilnikova
  • Fei Wan
  • Xiaoqing Chen
  • Jonathan Beesley
  • Christian F. Singer
  • Anne-Catharine Dressler
  • Daphne Gschwantler-Kaulich
  • Joanne L. Blum
  • Nadine Tung
  • Jeff Weitzel
  • Henry Lynch
  • Judy Garber
  • Douglas F. Easton
  • Susan Peock
  • Margaret Cook
  • Clare T. Oliver
  • Debra Frost
  • Don Conroy
  • D. Gareth Evans
  • Fiona Lalloo
  • Ros Eeles
  • Louise Izatt
  • Rosemarie Davidson
  • Carol Chu
  • Diana Eccles
  • Christina G. Selkirk
  • Mary Daly
  • Claudine Isaacs
  • Dominique Stoppa-Lyonnet
  • Olga M. Sinilnikova
  • Bruno Buecher
  • Muriel Belotti
  • Sylvie Mazoyer
  • Laure Barjhoux
  • Carole Verny-Pierre
  • Christine Lasset
  • Helene Dreyfus
  • Pascal Pujol
  • Marie-Agnes Collonge-Rame
  • Matti A. Rookus
  • Senno Verhoef
  • Mieke Kriege
  • Nicoline Hoogerbrugge
  • Margreet G. E. M. Ausems
  • Theo A. van Os
  • Juul Wijnen
  • Peter Devilee
  • Hanne E. J. Meijers-Heijboer
  • Marinus J. Blok
  • Tuomas Heikkinen
  • Heli Nevanlinna
  • Anna Jakubowska
  • Jan Lubinski
  • Tomasz Huzarski
  • Tomasz Byrski
  • Francine Durocher
  • Fergus J. Couch
  • Noralane M. Lindor
  • Xianshu Wang
  • Mads Thomassen
  • Susan Domchek
  • Kate Nathanson
  • M. A. Caligo
  • Annelie Liljegren
  • Per Karlsson
  • Patricia A. Ganz
  • Olufunmilayo I. Olopade
  • Gail Tomlinson
  • Susan Neuhausen
  • Antonis C. Antoniou
  • Georgia Chenevix-Trench
  • Timothy R. Rebbeck
External organisations
  • Uppsala University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • 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
Original languageEnglish
Pages (from-to)1032-1038
JournalCancer Epidemiology Biomarkers & Prevention
Issue number5
Publication statusPublished - 2011
Publication categoryResearch