Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers
Författare
Summary, in English
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.
Avdelning/ar
- Bröstcancer-genetik
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2011
Språk
Engelska
Sidor
1032-1038
Publikation/Tidskrift/Serie
Cancer Epidemiology Biomarkers & Prevention
Volym
20
Issue
5
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Association for Cancer Research
Ämne
- Cancer and Oncology
Nyckelord
- 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
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1538-7755