Pelttari, L.M., Khan, S. orcid.org/0000-0002-5138-1099 and et al. (2016) RAD51B in Familial Breast Cancer. PLoS One, 11 (5). e0153788. ISSN 1932-6203
Abstract
Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/). |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number YORKSHIRE CANCER RESEARCH S299 CANCER RESEARCH UK (CRUK) C5410/A7315. |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 May 2016 10:25 |
Last Modified: | 25 Oct 2016 09:10 |
Published Version: | http://dx.doi.org/10.1371/journal.pone.0153788 |
Status: | Published |
Publisher: | Public Library of Science |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pone.0153788 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97980 |
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