Journal article

Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D

Xin Yang, Honglin Song, Goska Leslie, Christoph Engel, Eric Hahnen, Bernd Auber, Judit Horvath, Karin Kast, Dieter Niederacher, Clare Turnbull, Richard Houlston, Helen Hanson, Chey Loveday, Jill S Dolinsky, Holly LaDuca, Susan J Ramus, Usha Menon, Adam N Rosenthal, Ian Jacobs, Simon A Gayther Show all

Journal of the National Cancer Institute | OXFORD UNIV PRESS INC | Published : 2020

Abstract

BACKGROUND: The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. METHODS: We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. RESULTS: Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% c..

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Grants

Awarded by Cancer Research UK


Awarded by Cancer Research Society


Awarded by Carlos III National Health Institute - FEDER funds a way to build Europe


Awarded by Spanish Instituto de Salud Carlos III - FEDER funds


Awarded by FEDER funds through Research Activity Intensification Program


Awarded by FEDER funds through Centro de Investigacion Biomedica en Red de Enferemdades Raras CIBERER


Awarded by Autonomous Government of Galicia


Awarded by European Union


Awarded by Spanish Instituto de Salud Carlos III, an initiative of the Spanish Ministry of economy and innovation - European regional development Feder Funds


Awarded by Canadian Institutes of Health Research Foundation Grant


Awarded by MRC


Awarded by European Union Seventh Framework Program (2007e2013)/European Research Council


Awarded by National Cancer Institute, Bethesda, MD


Awarded by Danish Cancer Society, Copenhagen, Denmark


Awarded by Research Council of Lithuania


Awarded by German Cancer Aid


Awarded by National Institutes of Health (NIH)


Awarded by US National Institutes of Health


Funding Acknowledgements

This work was supported by Cancer Research UK (C12292/A20861). ANR and UM were supported by the NIHR Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust and University College London. BR is supported by a Cancer Research Society grant (OG-24377). JB was supported by the Carlos III National Health Institute funded by FEDER funds a way to build Europe (PI16/11363). AO has received funding from the Spanish Instituto de Salud Carlos III (PI19/00640) supported by FEDER funds and Centro de Investigaci~on en Red de Enfermedades Raras. AV is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III, partially supported by FEDER funds through Research Activity Intensification Program (INT15/00070, INT16/00154, INT17/00133) and through Centro de Investigaci~on Biom~edica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018), Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundaci~on Mutua Madrile~na (call 2018). MH has received funding from the European Union's Horizon 2020 research and innovation program (634935) and from Spanish Instituto de Salud Carlos III (PI15/00059), an initiative of the Spanish Ministry of economy and innovation partially supported by European regional development Feder Funds. WDF was funded by a Canadian Institutes of Health Research Foundation Grant (FDN-148390). UM receives support from MRC core funding (MR_UU_12023). MT is funded by the European Union Seventh Framework Program (2007e2013)/European Research Council (310018) and by the NIHR Cambridge Biomedical Research Centre. UKFOCSS study data collection and sequencing was funded by the Eve Appeal and Cancer Research UK (C1005/A12677). Funding for MALOVA was provided by a research grant from the National Cancer Institute, Bethesda, MD (R01-CA61107); from the Danish Cancer Society, Copenhagen, Denmark (94 222 52); and the Mermaid I project. The CBCS study is supported by funding from the Capital Region of Denmark. The BFBOCC-LT study was supported by Research Council of Lithuania (SEN-16/2016). The German Consortium for Hereditary Breast and Ovarian Cancer is funded by the German Cancer Aid (110837, 70111850). FJC was supported in part by National Institutes of Health (NIH) grants R01 CA225662, P50 CA116201 and the Breast Cancer Research Foundation. Data for SEARCH was funded by Cancer Research UK (C490/A10119, C490/A10124, C490/A16561 and the Cambridge Cancer Centre) and the US National Institutes of Health (R01CA178535). The University of Cambridge has received salary support in respect of PDPP from the NHS in the East of England through the Clinical Academic Reserve. SAG is a recipient of the Barth Family Chair in Cancer Genetics. HEBCS is funded by Helsinki University Hospital Research Fund, the Sigrid Juselius Foundation and The Cancer Foundation Finland.