Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers
Open Access
- 1 January 2011
- journal article
- review article
- Published by Elsevier BV in Annals of Oncology
- Vol. 22 (suppl_1), i11-i17
- https://doi.org/10.1093/annonc/mdq660
Abstract
Germline mutations in BRCA1 and BRCA2 confer high risks of female breast and ovarian cancer. However, there is strong evidence that these risks are modified by other factors, including familial or genetic factors. Genome-wide association studies have identified several breast cancer genetic susceptibility variants in the general population that are also associated with breast cancer risk for mutation carriers. The patterns of association for these variants vary between BRCA1 and BRCA2 mutation carriers and this variation appears to be driven by their differential associations with breast cancer subtypes defined by estrogen receptor status. We review the latest evidence regarding genetic modifiers of cancer risk for female BRCA1 and BRCA2 mutation carriers emerging from candidate gene studies, variants found in genome-wide association studies (GWAS) to be associated with cancer risk in the general population and GWAS specifically in mutation carriers. We also discuss the implications of these findings for cancer risk prediction in these women. BRCA1 and BRCA2 mutation carriers could potentially be among the first groups of individuals for whom clinically applicable risk profiling could be developed using the common breast cancer susceptibility variants identified through GWAS.Keywords
This publication has 58 references indexed in Scilit:
- Pooled analysis indicates that the GSTT1 deletion, GSTM1 deletion, and GSTP1 Ile105Val polymorphisms do not modify breast cancer risk in BRCA1 and BRCA2 mutation carriersBreast Cancer Research and Treatment, 2009
- The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriersBreast Cancer Research and Treatment, 2009
- Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2Nature Genetics, 2009
- A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1)Nature Genetics, 2009
- Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1Nature Genetics, 2009
- Common Breast Cancer-Predisposition Alleles Are Associated with Breast Cancer Risk in BRCA1 and BRCA2 Mutation CarriersAmerican Journal of Human Genetics, 2008
- Variation of Breast Cancer Risk Among BRCA1/2 CarriersJama-Journal Of The American Medical Association, 2008
- Genome-wide association study identifies novel breast cancer susceptibility lociNature, 2007
- A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancerNature Genetics, 2007
- A common coding variant in CASP8 is associated with breast cancer riskNature Genetics, 2007