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. 2016 May 5;11(5):e0153788.
doi: 10.1371/journal.pone.0153788. eCollection 2016.

RAD51B in Familial Breast Cancer

Liisa M Pelttari  1 Sofia Khan  1 Mikko Vuorela  2 Johanna I Kiiski  1 Sara Vilske  1 Viivi Nevanlinna  1 Salla Ranta  1 Johanna Schleutker  3   4   5 Robert Winqvist  2   6 Anne Kallioniemi  3   7 Thilo Dörk  8 Natalia V Bogdanova  9 Jonine Figueroa  10 Paul D P Pharoah  11   12 Marjanka K Schmidt  13 Alison M Dunning  11 Montserrat García-Closas  10   14 Manjeet K Bolla  12 Joe Dennis  12 Kyriaki Michailidou  12 Qin Wang  12 John L Hopper  15 Melissa C Southey  16 Efraim H Rosenberg  13 Peter A Fasching  17   18 Matthias W Beckmann  17 Julian Peto  19 Isabel Dos-Santos-Silva  19 Elinor J Sawyer  20 Ian Tomlinson  21 Barbara Burwinkel  22   23 Harald Surowy  22   23 Pascal Guénel  24   25 Thérèse Truong  24   25 Stig E Bojesen  26   27   28 Børge G Nordestgaard  27   28 Javier Benitez  29   30 Anna González-Neira  29 Susan L Neuhausen  31 Hoda Anton-Culver  32 Hermann Brenner  33   34   35 Volker Arndt  33 Alfons Meindl  36 Rita K Schmutzler  37   38   39 Hiltrud Brauch  34   40   41 Thomas Brüning  42 Annika Lindblom  43 Sara Margolin  44 Arto Mannermaa  45   46   47 Jaana M Hartikainen  45   46   47 Georgia Chenevix-Trench  48 kConFab/AOCS InvestigatorsLaurien Van Dyck  49   50 Hilde Janssen  51 Jenny Chang-Claude  52   53 Anja Rudolph  52 Paolo Radice  54 Paolo Peterlongo  55 Emily Hallberg  56 Janet E Olson  56 Graham G Giles  15   57 Roger L Milne  15   57 Christopher A Haiman  58 Fredrick Schumacher  58 Jacques Simard  59 Martine Dumont  59 Vessela Kristensen  60   61   62 Anne-Lise Borresen-Dale  60   61 Wei Zheng  63 Alicia Beeghly-Fadiel  63 Mervi Grip  64 Irene L Andrulis  65   66 Gord Glendon  65 Peter Devilee  67   68 Caroline Seynaeve  69 Maartje J Hooning  69 Margriet Collée  70 Angela Cox  71 Simon S Cross  72 Mitul Shah  11 Robert N Luben  73 Ute Hamann  74 Diana Torres  74   75 Anna Jakubowska  76 Jan Lubinski  76 Fergus J Couch  77 Drakoulis Yannoukakos  78 Nick Orr  79 Anthony Swerdlow  14   80 Hatef Darabi  81 Jingmei Li  81 Kamila Czene  81 Per Hall  81 Douglas F Easton  11   12 Johanna Mattson  82 Carl Blomqvist  82 Kristiina Aittomäki  83 Heli Nevanlinna  1
Affiliations

RAD51B in Familial Breast Cancer

Liisa M Pelttari et al. PLoS One. .

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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Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following competing interests: A. Mannermaa is a member of the PLOS ONE Editorial Board. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria.

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