RAD51B in familial breast cancer

Liisa M. Pelttari, Sofia Khan, Mikko Vuorela, Johanna I. Kiiski, Sara Vilske, Viivi Nevanlinna, Salla Ranta, Johanna Schleutker, Robert Winqvist, Anne Kallioniemi, Thilo Dörk, Natalia V. Bogdanova, Jonine Figueroa, Paul D.P. Pharoah, Marjanka K. Schmidt, Alison M. Dunning, Montserrat García-Closas, Manjeet K. Bolla, Joe Dennis, Kyriaki MichailidouQin Wang, John L. Hopper, Melissa C. Southey, Efraim H. Rosenberg, Peter A. Fasching, Matthias W. Beckmann, Julian Peto, Isabel dos-Santos-Silva, Elinor J. Sawyer, Ian Tomlinson, Barbara Burwinkel, Harald Surowy, Pascal Guénel, Thérèse Truong, Stig E. Bojesen, Børge G. Nordestgaard, Javier Benitez, Anna González-Neira, Susan L. Neuhausen, Hoda Anton-Culver, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K. Schmutzler, Hiltrud Brauch, Thomas Brüning, Annika Lindblom, Sara Margolin, Arto Mannermaa, Jaana M. Hartikainen, Georgia Chenevix-Trench, kConFab/AOCS Investigators, Laurien Van Dyck, Hilde Janssen, Jenny Chang-Claude, Anja Rudolph, Paolo Radice, Paolo Peterlongo, Emily Hallberg, Janet E. Olson, Graham G. Giles, Roger L. Milne, Christopher A. Haiman, Fredrick Schumacher, Jacques Simard, Martine Dumont, Vessela Kristensen, Anne Lise Borresen-Dale, Wei Zheng, Alicia Beeghly-Fadiel, Mervi Grip, Irene L. Andrulis, Gord Glendon, Peter Devilee, Caroline Seynaeve, Maartje J. Hooning, Margriet Collée, Angela Cox, Simon S. Cross, Mitul Shah, Robert N. Luben, Ute Hamann, Diana Torres, Anna Jakubowska, Jan Lubinski, Fergus J. Couch, Drakoulis Yannoukakos, Nick Orr, Anthony Swerdlow, Hatef Darabi, Jingmei Li, Kamila Czene, Per Hall, Douglas F. Easton, Johanna Mattson, Carl Blomqvist, Kristiina Aittomäki, Heli Nevanlinna, Frank Firgaira, Scott Grist, Eric Haan, Ram Seshadri, Pamela Sykes, D. Henderson

    Research output: Contribution to journalArticlepeer-review

    19 Citations (Scopus)
    4 Downloads (Pure)


    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 × 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 × 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.

    Original languageEnglish
    Article numbere0153788
    Number of pages18
    JournalPLoS One
    Issue number5
    Publication statusPublished - 5 May 2016

    Bibliographical note

    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.


    • RAD51B
    • breast cancer
    • familial breast cancer
    • Finland
    • Finnish people
    • Genetic causes of cancer
    • Variant genotypes
    • Introns
    • Ovarian cancer
    • Haplotypes


    Dive into the research topics of 'RAD51B in familial breast cancer'. Together they form a unique fingerprint.

    Cite this