Journal article
Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases
G Figlioli, A Billaud, Q Wang, MK Bolla, J Dennis, M Lush, A Kvist, MA Adank, TU Ahearn, NN Antonenkova, P Auvinen, S Behrens, M Bermisheva, NV Bogdanova, SE Bojesen, B Bonanni, T Brüning, NJ Camp, A Campbell, JE Castelao Show all
Cancers | MDPI | Published : 2023
Abstract
FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencie..
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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] and an institutional grant of the Dutch Cancer Society and of the Dutch Ministry of Health, Welfare and Sport. 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). The CAMA study was funded by Consejo Nacional de Ciencia y Tecnologia (CONACyT) (SALUD-2002-C01-7462). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). 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 CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev and Gentofte Hospital.r 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 (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837 and 70114178, coordinator: Rita K. Schmutzler, Cologne) and the Federal Ministry of Education and Research, Germany (grant no 01GY1901). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE-Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). 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 German Research Foundation (DFG Do761/15-1), 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, NKI 12535, 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 the German Research Foundation (DFG Do761/151), a grant from the Friends of Hannover Medical School, and by the Rudolf Bartling Foundation. The HUBCS was supported by German Research Foundation (DFG Do761/15-1), 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.r 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 (No AAAAA-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 was 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). G.C.T. and P.W. were 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 Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. 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-L Borresen-Dale and V.N. Kristensen) and grant 193387/H10 (to A-L Borresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A-L Borresen-Dale) and the Norwegian Cancer Society (to A-L Borresen-Dale and V.N. Kristensen). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Ontario Familial Breast Cancer Registry (OFBCR) was supported by grant U01CA164920 from the USA National Cancer Institute of the National Institutes of Health.r The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. 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 2004-3124, 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 was 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 was supported by the DKFZ. 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 N.J. Camp) 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). Partial support for all datasets within the UPDB was provided by the University of Utah HCI and the HCI Cancer Center Support grant, P30 CA2014 from the NCI. The UCR is funded by the NCI's SEER Program, Contract No. HHSN261201800016I, the US Centers for Disease Control and Prevention's National Program of Cancer Registries, Cooperative Agreement No. NU58DP006320, with additional support from the University of Utah and Huntsman Cancer Foundation.