No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing

Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Dennis J, Ahmad J, Thompson ER, Damiola F, Pertesi M, Voegele C, Mebirouk N, Robinot N, Durand G, Forey N, Luben RN, Ahmed S, Aittomaki K, Anton-Culver H, Arndt V, Baynes C, Beckmann M, Benitez J, Van Den Berg D, Blot WJ, Bogdanova NV, Bojesen SE, Brenner H, Chang-Claude J, Chia KS, Choi JY, Conroy DM, Cox A, Cross SS, Czene K, Darabi H, Devilee P, Eriksson M, Fasching P, Figueroa J, Flyger H, Fostira F, Garcia-Closas M, Giles GG, Glendon G, Gonzalez-Neira A, Guenel P, Haiman CA, Hall P, Hart SN, Hartman M, Hooning MJ, Hsiung CN, Ito H, Jakubowska A, James PA, John EM, Johnson N, Jones M, Kabisch M, Kang D, Kosma VM, Kristensen V, Lambrechts D, Li N, Lindblom A, Long J, Lophatananon A, Lubinski J, Mannermaa A, Manoukian S, Margolin S, Matsuo K, Meindl A, Mitchell G, Muir K, Nevelsteen I, Van Den Ouweland A, Peterlongo P, Phuah SY, Pylkas K, Rowley SM, Sangrajrang S, Schmutzler RK, Shen CY, Shu XO, Southey MC, Surowy H, Swerdlow A, Teo SH, Tollenaar RAEM, Tomlinson I, Torres D, Truong T, Vachon C, Verhoef S, Wong-Brown M, Zheng W, Zheng Y, Nevanlinna H, Scott RJ, Andrulis IL, Wu AH, Hopper JL, Couch FJ, Winqvist R, Burwinkel B, Sawyer EJ, Schmidt MK, Rudolph A, Doerk T, Brauch H, Hamann U, Neuhausen SL, Milne RL, Fletcher O, Pharoah PDP, Campbell IG, Dunning AM, Le Calvez-Kelm F, Goldgar DE, Tavtigian SV, Chenevix-Trench G (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 53

Pages Range: 298-309

Journal Issue: 5

DOI: 10.1136/jmedgenet-2015-103529

Abstract

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.

Authors with CRIS profile

Involved external institutions

International Agency for Research on Cancer (IARC) France (FR) University of California Irvine United States (USA) (US) University of Cambridge United Kingdom (GB) Helsingin yliopisto / University of Helsinki Finland (FI) Mines ParisTech / École Nationale Supérieure des Mines de Paris (ENSMP) France (FR) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) The Institute of Cancer Research (ICR) United Kingdom (GB) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Vanderbilt University United States (USA) (US) University of Eastern Finland Finland (FI) Technische Universität München (TUM) Germany (DE) Peter MacCallum Cancer Centre Australia (AU) University of Malaya (UM) / Universiti Malaya Malaysia (MY) The University of Melbourne Australia (AU) University of Warwick United Kingdom (GB) University of Utah United States (USA) (US) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) NordLab Finland (FI) IFOM - FIRC Institute of Molecular Oncology Italy (IT) University of Oxford United Kingdom (GB) Leiden University Netherlands (NL) Mount Sinai Hospital (MSH) Canada (CA) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Universitätsklinikum Köln Germany (DE) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Karolinska Institute Sweden (SE) China Medical University (CMU) / 中國醫藥大學 Taiwan (TW) Aichi Cancer Center Research Institute Japan (JP) National Cancer Institute (NCI) United States (USA) (US) University of Sheffield United Kingdom (GB) National University of Singapore (NUS) Singapore (SG) Academia Sinica / 中央研究院 Taiwan (TW) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Mayo Clinic United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud France (FR) John Hunter Hospital Australia (AU) Antoni van Leeuwenhoek Netherlands (NL) Cancer Council Victoria Australia (AU) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Beckman Research Institute of City of Hope (BRI) United States (USA) (US) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) Guy's and St Thomas' (NHS Foundation Trust) United Kingdom (GB) Centre Léon-Bérard (UNICANCER) France (FR) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Shanghai Center For Disease Control And Prevention (SCDC) China (CN) Copenhagen University Hospital Denmark (DK) Herlev Hospital Denmark (DK) Cancer Prevention Institute of California (CPIC) United States (USA) (US)

How to cite

APA:

Easton, D.F., Lesueur, F., Decker, B., Michailidou, K., Li, J., Allen, J.,... Chenevix-Trench, G. (2016). No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing. Journal of Medical Genetics, 53(5), 298-309. https://dx.doi.org/10.1136/jmedgenet-2015-103529

MLA:

Easton, Douglas F., et al. "No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing." Journal of Medical Genetics 53.5 (2016): 298-309.

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