Journal article
Risk of contralateral breast cancer associated with common variants in BRCA1 and BRCA2: potential modifying effect of BRCA1/BRCA2 mutation carrier status
Breast cancer research and treatment, Vol.127(3), pp.819-829
06/2011
DOI: 10.1007/s10549-010-1285-1
PMCID: PMC3234998
PMID: 21161372
Abstract
Rare deleterious mutations in BRCA1 and BRCA2 are associated with an elevated risk of breast and ovarian cancer. Whether or not common variants in these genes are independently associated with risk of breast cancer remains unclear. In this study, we included 632 Caucasian women with asynchronous contralateral breast cancer (CBC, cases) and 1,221 women with unilateral breast cancer (UBC, controls) from the WECARE (Women's Environment, Cancer and Radiation Epidemiology) Study. BRCA1 and BRCA2 deleterious mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing, yielding including 88 BRCA1 and 60 BRCA2 deleterious mutation carriers. We also genotyped samples on the Illumina Omni1-Quad platform. We assessed the association between CBC risk and common (minor allele frequency (MAF) > 0.05) single-nucleotide polymorphisms (SNPs) in BRCA1 (n SNPs = 22) and BRCA2 (n SNPs = 30) and haplotypes using conditional logistic regression accounting for BRCA1/BRCA2 mutation status. We found no significant associations between any single-SNPs or haplotypes of BRCA1 or BRCA2 and risk of CBC among all women. When we stratified by BRCA1 and BRCA2 mutation carrier status, we found suggestive evidence that risk estimates for selected SNPs in BRCA1 (rs8176318, rs1060915, and rs16940) and BRCA2 (rs11571686, rs206115, and rs206117) may differ in non-carriers and carriers of deleterious mutations in BRCA1 and BRCA2. One common haplotype on BRCA1 was inversely significantly associated with risk only among non-BRCA1 and BRCA2 carriers. The association between common variants in BRCA1 and BRCA2 and risk of CBC may differ depending on BRCA1 and BRCA2 mutation carrier status.
Details
- Title: Subtitle
- Risk of contralateral breast cancer associated with common variants in BRCA1 and BRCA2: potential modifying effect of BRCA1/BRCA2 mutation carrier status
- Creators
- Jane C Figueiredo - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Harlyne J Norris Cancer Research Tower, 1450 Biggy Street Room 1509J, Los Angeles, CA 90033, USA. janefigu@usc.eduJennifer D BrooksDavid V ContiJenny N PoynterSharon N TeraokaKathleen E MaloneLeslie BernsteinWon D LeeDavid J DugganAshley SiniardPatrick ConcannonMarinela CapanuCharles F LynchJørgen H OlsenRobert W HaileJonine L Bernstein
- Resource Type
- Journal article
- Publication Details
- Breast cancer research and treatment, Vol.127(3), pp.819-829
- DOI
- 10.1007/s10549-010-1285-1
- PMID
- 21161372
- PMCID
- PMC3234998
- NLM abbreviation
- Breast Cancer Res Treat
- ISSN
- 1573-7217
- eISSN
- 1573-7217
- Publisher
- Netherlands
- Grant note
- R01 CA129639 / NCI NIH HHS R01 CA097397 / NCI NIH HHS R01 CA097397-05 / NCI NIH HHS U01 CA083178 / NCI NIH HHS R01 AG014358 / NIA NIH HHS
- Language
- English
- Date published
- 06/2011
- Academic Unit
- Epidemiology
- Record Identifier
- 9983995140702771
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