RAD51B in Familial Breast Cancer

Pelttari LM, Khan S, Vuorela M, Kiiski JI, Vilske S, Nevanlinna V, Ranta S, Schleutker J, Winqvist R, Kallioniemi A, Doerk T, Bogdanova NV, Figueroa J, Pharoah PDP, Schmidt MK, Dunning AM, Garcia-Closas M, Bolla MK, Dennis J, Michailidou K, Wang Q, Hopper JL, Southey MC, Rosenberg EH, Fasching P, Beckmann M, Peto J, Dos-Santos-Silva I, Sawyer EJ, Tomlinson I, Burwinkel B, Surowy H, Guenel P, Truong T, Bojesen SE, Nordestgaard BG, Benitez J, Gonzalez-Neira A, Neuhausen SL, Anton-Culver H, Brenner H, Arndt V, Meindl A, Schmutzler RK, Brauch H, Bruening T, Lindblom A, Margolin S, Mannermaa A, Hartikainen JM, Chenevix-Trench G, Van Dyck L, Janssen H, Chang-Claude J, Rudolph A, Radice P, Peterlongo P, Hallberg E, Olson JE, Giles GG, Milne RL, Haiman CA, Schumacher F, Simard J, Dumont M, Kristensen V, Borresen-Dale AL, Zheng W, Beeghly-Fadiel A, Grip M, Andrulis IL, Glendon G, Devilee P, Seynaeve C, Hooning MJ, Collee M, Cox A, Cross SS, Shah M, Luben RN, Hamann U, Torres D, Jakubowska A, Lubinski J, Couch FJ, Yannoukakos D, Orr N, Swerdlow A, Darabi H, Li J, Czene K, Hall P, Easton DF, Mattson J, Blomqvist C, Aittomaki K, Nevanlinna H (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 11

Journal Issue: 5

DOI: 10.1371/journal.pone.0153788

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.

Authors with CRIS profile

Involved external institutions

Helsingin yliopisto / University of Helsinki Finland (FI) Oulun Yliopisto / University of Oulo Finland (FI) University of Tampere (UTA) / Tampereen yliopisto (Tay) Finland (FI) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University of Cambridge United Kingdom (GB) The University of Melbourne Australia (AU) Antoni van Leeuwenhoek Netherlands (NL) London School of Hygiene and Tropical Medicine United Kingdom (GB) King’s College London United Kingdom (GB) University of Oxford United Kingdom (GB) Ruprecht-Karls-Universität Heidelberg Germany (DE) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) Copenhagen University Hospital Denmark (DK) Ruhr-Universität Bochum (RUB) Germany (DE) Karolinska Institute Sweden (SE) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Mount Sinai Hospital (MSH) Canada (CA) Leiden University Netherlands (NL) Erasmus University Medical Center (MC) Netherlands (NL) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) University of Sheffield United Kingdom (GB) National Cancer Institute (NCI) United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Beckman Research Institute of City of Hope (BRI) United States (USA) (US) University of California Irvine United States (USA) (US) Technische Universität München (TUM) Germany (DE) Universitätsklinikum Köln Germany (DE) Mayo Clinic United States (USA) (US) University of Southern California (USC) United States (USA) (US) Université Laval (UL) Canada (CA) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Vanderbilt University United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) The Institute of Cancer Research (ICR) United Kingdom (GB) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI)

How to cite

APA:

Pelttari, L.M., Khan, S., Vuorela, M., Kiiski, J.I., Vilske, S., Nevanlinna, V.,... Nevanlinna, H. (2016). RAD51B in Familial Breast Cancer. PLoS ONE, 11(5). https://dx.doi.org/10.1371/journal.pone.0153788

MLA:

Pelttari, Liisa M., et al. "RAD51B in Familial Breast Cancer." PLoS ONE 11.5 (2016).

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