Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants

Accepted/In Press date: 25 August 2021

e-pub ahead of print date: 30 November 2021

Published date: 5 January 2022

Additional Information: A correction has been attached to this output located at 10.1016/j.gim.2022.08.005 Funding Information: We thank the families who participated in the study. This work was funded by grants from the French National Cancer Institute INCa BCB (2013-1-BCB-01-531 ICH-1) and from the French Ligue contre le cancer 92. A.E.T. wishes to thank Hayley Cassingham, Leigha Senter, and Kevin Sweet who were instrumental in consenting of study participants and data collection and funding from The Ohio State University Comprehensive Cancer Center. Funding Information: The work of A.B.S. and M.T.P. was supported by the Australian National Health and Medical Research funding (ID1177524). E.I.P. was supported by Barretos Cancer Hospital, FINEP - CT-INFRA (02/2010), and a National Council of Technological and Scientific Development (CNPq) scholarship. We wish to thank members of the Center of Molecular Diagnosis, Oncogenetics Department, and Molecular Oncology Research Center of Barretos Cancer Hospital for their contributions to the study. M.d.l.H was supported by grants from the Spanish Ministry of Science and Innovation, Plan Nacional de I+D+I 2013-2016, ISCIII (PI15/00059 and PI20/00110) co-funded by FEDER from Regional Development European Funds (European Union). A.V. was supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII) through Research Activity Intensification Program (contract grants: INT15/00070, INT16/00154, INT17/00133, INT20/00071) and through Centro de Investigación Biomédica en Red de Enfermedades Raras (ACCI 2016: ER17P1AC7112/2018); by Autonomous Government of Galicia (Consolidation and structuring program: IN607B); and by the Fundación Mutua Madrileña (call 2018).We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan and Bogota, Colombia. I.L.A., M.B.T., and E.M.J. were supported by grant UM1 CA164920 from the US National Cancer Institute. 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 nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast Cancer Family Registry. P.R. was supported by funds from the Italian Association for Cancer Research (IG number 22093).The work of P.P. was supported by the Italian Association for Cancer Research funding IG-16732. B.P. was supported by the DSM-UniTO Excellence Project n. D15D18000410001. The contribution of F.J.C. was supported by National Institutes of Health grants R35 CA253187, R01 CA225662, and R01 CA116167; a specialized program of research excellence in breast cancer (P50 CA116201); and the Breast Cancer Research Foundation. S.D. was supported by the Breast Cancer Research Foundation.The work of A.C.A., G.L., and X.Y. were supported by Cancer Research United Kingdom grants C12292/A20861 and PPRPGM-Nov20/100002. S.M.C. thanks the clinicians and biologists ( Supplemental Table 2 ) involved in the French Unicancer Genetic Group for their cooperation. Funding Information: The work of A.B.S. and M.T.P. was supported by the Australian National Health and Medical Research funding (ID1177524). E.I.P. was supported by Barretos Cancer Hospital, FINEP - CT-INFRA (02/2010), and a National Council of Technological and Scientific Development (CNPq) scholarship. We wish to thank members of the Center of Molecular Diagnosis, Oncogenetics Department, and Molecular Oncology Research Center of Barretos Cancer Hospital for their contributions to the study. M.d.l.H was supported by grants from the Spanish Ministry of Science and Innovation, Plan Nacional de I+D+I 2013-2016, ISCIII (PI15/00059 and PI20/00110) co-funded by FEDER from Regional Development European Funds (European Union). A.V. was supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII) through Research Activity Intensification Program (contract grants: INT15/00070, INT16/00154, INT17/00133, INT20/00071) and through Centro de Investigación Biomédica en Red de Enfermedades Raras (ACCI 2016: ER17P1AC7112/2018); by Autonomous Government of Galicia (Consolidation and structuring program: IN607B); and by the Fundación Mutua Madrileña (call 2018).We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan and Bogota, Colombia. I.L.A. M.B.T. and E.M.J. were supported by grant UM1 CA164920 from the US National Cancer Institute. 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 nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast Cancer Family Registry. P.R. was supported by funds from the Italian Association for Cancer Research (IG number 22093).The work of P.P. was supported by the Italian Association for Cancer Research funding IG-16732. B.P. was supported by the DSM-UniTO Excellence Project n. D15D18000410001. The contribution of F.J.C. was supported by National Institutes of Health grants R35 CA253187, R01 CA225662, and R01 CA116167; a specialized program of research excellence in breast cancer (P50 CA116201); and the Breast Cancer Research Foundation. S.D. was supported by the Breast Cancer Research Foundation.The work of A.C.A. G.L. and X.Y. were supported by Cancer Research United Kingdom grants C12292/A20861 and PPRPGM-Nov20/100002. S.M.C. thanks the clinicians and biologists ( Supplemental Table 2) involved in the French Unicancer Genetic Group for their cooperation. We thank the families who participated in the study. This work was funded by grants from the French National Cancer Institute INCa BCB (2013-1-BCB-01-531 ICH-1) and from the French Ligue contre le cancer 92. A.E.T. wishes to thank Hayley Cassingham, Leigha Senter, and Kevin Sweet who were instrumental in consenting of study participants and data collection and funding from The Ohio State University Comprehensive Cancer Center. Conceptualization: D.E.G. A.B.S. F.J.C. R.S. B.W.; Data Curation: A.E.T. P.P. P.R. T.C. L.L. E.I.P. A.K. H.T. P.J. B.W. C.E. M.T. T.H. E.J. M.B.T. M.T.P. I.A. S.C. C.L. H.N. J.G. M.M. M.S. A.S. A.Z. A.G. U.H. S.D. S.N. S.M.C. B.P. M.C.S. J.K. G.C.T. J.H. P.M. R.J. L.K. D.Y. S.E.B. L.V. A.V. T.S. D.E.G. C.J.V.A. G.L. A.T. L.F; Formal Analysis: H.L. D.E.G; Funding Acquisition: F.J.C. A.S.; Methodology: D.E.G. A.C.A. X.Y. M.T.P. H.L.; Writing-original draft: D.E.G.; Writing-review and editing: H.L. C.E. M.d.l.H. P.P. D.Y. L.L. P.R. M.T. T.V.O.H. A.M.G. H.R.N. S.M.C. A.Z. A.B. A.S. A.T. M.T.P. A.C.A. G.L. X.Y. G.C.T. T.C. A.K. I.S.P. C.K.L. E.M.J. M.B.T. J.L.H. M.C.S. I.L.A. M.T. R.J. S.E.B. L.K. L.V. U.H. A.V. E.I.P. J.G. M.M. C.J.V.A. L.F. M.H.G. T.S. P.M. A.E.T. S.M.D. P.J. H.T. D.M.E. S.M.N. S.M. B.P. M.A.C. C.L. J.K. B.W. F.J.C. R.S. D.E.G. ENIGMA Consortium, CIMBA Consortium. This study was covered under Amendment to Project P1051 (PI: A.BS.) approved by the Human Research Ethics Committee at QIMR Berghofer, Brisbane, Australia, on October 7, 2020. All patients gave consent to have their data used for research purposes, and all studies received local Ethics Committee approvals. Data from all centers were de-identified before analysis at the coordinating center. BRCA Exchange. Accessed February 15, 2021. https://brcaexchange.org/. HCI Priors database. Huntsman Cancer Institute. Accessed February 15, 2021. http://priors.hci.utah.edu/PRIORS/BRCA/viewer.php?gene=BRCA1. Publisher Copyright: © 2021 American College of Medical Genetics and Genomics

Related URLs:

• http://10.1016/j.gim.2022.08.005

Keywords: BRCA1, BRCA2, Cancer risks, Missense variants

Local EPrints ID: 454437

URI: http://eprints.soton.ac.uk/id/eprint/454437

DOI: doi:10.1016/j.gim.2021.08.016

ISSN: 1098-3600

PURE UUID: bc29f47d-b475-402b-983c-569206f7ac36

ORCID for Diana M. Eccles: orcid.org/0000-0002-9935-3169

Date deposited: 09 Feb 2022 17:39

Last modified: 18 Mar 2024 02:37