Journal article
FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women
Gisella Figlioli, Amandine Billaud, Thomas U Ahearn, Natalia N Antonenkova, Heiko Becher, Matthias W Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Marinus J Blok, Natalia V Bogdanova, Bernardo Bonanni, Barbara Burwinkel, Nicola J Camp, Archie Campbell, Jose E Castelao, Melissa H Cessna, Stephen J Chanock, Kamila Czene, Peter Devilee Show all
European Journal of Human Genetics | Springer Nature [academic journals on nature.com] | Published : 2023
Abstract
Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested..
View full abstractRelated Projects (4)
Grants
Awarded by Associazione Italiana Ricerca sul Cancro (AIRC)
Awarded by European Union's Horizon 2020 Research and Innovation Programme
Awarded by European Union Horizon 2020 research and innovation program BRIDGES
Awarded by Wellcome Trust
Awarded by Dutch Cancer Society
Awarded by Accion Estrategica de Salud del Instituto de Salud Carlos III
Awarded by FEDER
Awarded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud
Awarded by Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain
Awarded by Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I+ D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain
Awarded by Fondo de Investigacion Sanitario
Awarded by NIHR
Awarded by NIHR Manchester Biomedical Research Centre
Awarded by German Cancer Aid
Awarded by Federal Ministry of Education and Research (BMBF), Germany
Awarded by Chief Scientist Office of the Scottish Government Health Directorates
Awarded by Scottish Funding Council
Awarded by Deutsche Krebshilfe e. V.
Awarded by Netherlands Organisation of Scientific Research grant
Awarded by Pink Ribbon
Awarded by BBMRI grant
Awarded by German Federal Ministry of Research and Education
Awarded by Russian Foundation for Basic Research
Awarded by Government of Russian Federation
Awarded by Ministry of Science and Higher Education of the Russian Federation
Awarded by United States Army Medical Research and Materiel Command
Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by Deutsche Krebshilfe e.V.
Awarded by Federal Ministry of Education and Research (BMBF) Germany
Awarded by Cyprus Research Promotion Foundation
Awarded by Australian National Health and Medical Research Council
Awarded by Research Council of Norway grant
Awarded by South Eastern Norway Health Authority
Awarded by USA National Cancer Institute of the National Institutes of Health
Awarded by Biobanking and Biomolecular Resources Research Infrastructure
Awarded by Cancer Research UK
Awarded by Swedish Research Council
Awarded by National Cancer Institute (NCI)
Awarded by NCI
Awarded by NCI's SEER Program
Awarded by US Center for Disease Control and Prevention's National Program of Cancer Registries
Awarded by JTC 2012 Cancer
Funding Acknowledgements
[ "This study was supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG22860) to Paolo Peterlongo and by a fellowship from Fondazione Umberto Veronesi to Gisella Figlioli. BCAC is funded by the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and the PERSPECTIVE I&I project, funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministere de l'Economie et de l'Innovation du Quebec through Genome Quebec, the Quebec Breast Cancer Foundation. The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Additional funding for BCAC is provided via the Confluence project which is funded with intramural funds from the National Cancer Institute Intramural Research Program, National Institutes of Health. The BRIDGES panel sequencing was supported by the European Union Horizon 2020 research and innovation program BRIDGES (grant number, 634935) and the Wellcome Trust (v203477/Z/16/Z). The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. The BREast Oncology GAlician Network (BREOGAN) is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado and FEDER PI17/00918/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I+ D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070). FHRISK and PROCAS are funded from NIHR grant PGfAR 0707-10031. DGE, AH and WGN are supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). The GC-HBOC is funded by the German Cancer Aid (#110837, #70111850, #70114178, coordinator: RKS, Cologne) and the Federal Ministry of Education and Research (BMBF), Germany (grant no 01GY1901).", "LIFE Leipzig Research Center for Civilisation Diseases, Universitat Leipzig, is funded by means of the European Union, by the European Regional Development Fund (ERDF), and by means of the Free State of Saxony within the framework of the excellence initiative. The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Johanniter GmbH Bonn, Johanniter Krankenhaus, Bonn, Germany. Generation Scotland (GENSCOT) received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award \"STratifying Resilience and Depression Longitudinally\" (STRADL) Reference 104036/Z/14/Z). Funding for identification of cases and contribution to BCAC funded in part by the Wellcome Trust Seed Award \"Temporal trends in incidence and mortality of molecular subtypes of breast cancer to inform public health, policy and prevention\" Reference 207800/Z/17/Z. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Hospital Research Fund, the Sigrid Juselius Foundation and the Cancer Foundation Finland. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), B.M. was supported by grant 17-44-020498, 17-29-06014 of the Russian Foundation for Basic Research, D.P. was supported by grant 18-29-09129 of the Russian Foundation for Basic Research, E.K was supported by the mega grant from the Government of Russian Federation (2020-220-08-2197), and the study was performed as part of the assignment of the Ministry of Science and Higher Education of the Russian Federation (.....-.16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (VTR) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland.", "kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). GCT and PW are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. The MASTOS study was supported by \"Cyprus Research Promotion Foundation\" grants 0104/13 and 0104/17, and the Cyprus Institute of Neurology and Genetics. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC). The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The NBCS has received funding from the K.G. Jebsen Centre for Breast Cancer Research; the Research Council of Norway grant 193387/V50 (to A-LB-D and VNK) and grant 193387/H10 (to A-LB-D and VNK), South Eastern Norway Health Authority (grant 39346 to A-LB-D) and the Norwegian Cancer Society (to A-LB-D and VNK). The Ontario Familial Breast Cancer Registry (OFBCR) was supported by grant U01CA164920 from the USA National Cancer Institute of the National Institutes of Health. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The RBCS was funded by the Dutch Cancer Society (DDHK 20043124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SKKDKFZS is supported by the DKFZ.", "The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council (VR 2017-00644) grant for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER). The SZBCS was supported by Grant PBZ_KBN_122/P05/2004 and the program of the Minister of Science and Higher Education under the name \"Regional Initiative of Excellence\" in 2019-2022 project number 002/RID/2018/19 amount of financing 12,000,000 PLN. UBCS was supported by funding from National Cancer Institute (NCI) grant R01 CA163353 (to NJC) and the Women's Cancer Center at the Huntsman Cancer Institute (HCI). Data collection for UBCS was supported by the Utah Population Database (UPDB) and Utah Cancer Registry (UCR). The UPDB is supported by HCI (including Huntsman Cancer Foundation, HCF), the University of Utah, and NCI grant P30 CA2014. The UCR is funded by the NCI's SEER Program, Contract No. HHSN261201800016I, the US Center for Disease Control and Prevention's National Program of Cancer Registries (Cooperative Agreement No. NU58DP006320), the University of Utah, and HCF." ]