Journal
GENETICS IN MEDICINE
Volume 23, Issue 9, Pages 1726-1737Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/s41436-021-01198-7
Keywords
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Categories
Funding
- Alpe d'HuZes/Dutch Cancer Society (KWF Kankerbestrijding) project [6253]
- Dutch Cancer Society (KWF Kankerbestrijding) project [UL2014-7473]
- Cancer Research-UK [C12292/A20861, C12292/A11174]
- iCOGS: the European Community's Seventh Framework Programme [223175 (HEALTH-F2-2009223175)]
- Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A 10710, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565, C1287/A16563, C5047/A8385]
- National Institutes of Health [CA128978]
- Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]
- Department of Defence [W81XWH-10-1-0341]
- Canadian Institutes of Health Research (CIHR) [CRN87521]
- Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]
- Komen Foundation for the Cure
- Breast Cancer Research Foundation
- Ovarian Cancer Research Fund
- Government of Canada through Genome Canada
- Government of Canada through Canadian Institutes of Health Research
- Ministere de l'Economie, de la Science et de l'Innovation du Quebec through Genome Quebec
- Quebec Breast Cancer Foundation
- NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative
- Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH) [U19 CA148065, X01HG007492]
- National Cancer Institute [BCFR: UM1 CA164920, RC4CA153828]
- BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant [SEN-18/2015]
- BIDMC: Breast Cancer Research Foundation
- BMBSA: Cancer Association of South Africa
- Morris and Horowitz Families Professorship
- FEDER funds [PI16/00440]
- Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2014-57680-R]
- Spanish Research Network on Rare diseases (CIBERER)
- National Cancer Institute of the National Institutes of Health [R25CA112486]
- Office of the Director, National Institutes of Health [RC4CA153828]
- CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC
- IG2015) [16732]
- Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research Technology [SYN11_10_19 NBCA]
- Investing in knowledge society through the European Social Fund
- DFKZ: German Cancer Research Center
- EMBRACE: Cancer Research UK [C1287/A10118, C1287/A11990]
- NIHR
- NCI [R01 CA214545]
- University of Kansas Cancer Center [P30 CA168524]
- Kansas Institute for Precision Medicine [P20 GM130423]
- Kansas Bioscience Authority Eminent Scholar Program
- Spanish Health Research Foundation
- Instituto de Salud Carlos III (ISCIII) - FEDER funds through Research Activity Intensification Program [INT15/00070, INT16/00154, INT17/00133]
- FEDER funds through Centro de Investigacion Biomedica en Red de Enferemdades Raras CIBERER [ACCI 2016: ER17P1AC7112/2018]
- Autonomous Government of Galicia (Consolidation and structuring program) [IN607B]
- Fundacion Mutua Madrilena
- German Cancer Aid [110837, 70111850]
- Ministry for Innovation, Science and Research of the State of North Rhine-Westphalia [3238.0302.16.02-132142]
- French National Institute of Cancer (INCa, PHRC Ile de France) [AOR 01 082, 2001-2003, 2013-1-BCB-01ICH-1]
- Association Le cancer du sein, parlons-en! Award (2004)
- Association for International Cancer Research (2008-2010)
- Foundation ARC pour la recherche sur le cancer [PJA 20151203365]
- Canadian Institute of Health Research
- INCa [SHS-E-SP 18-015]
- GEORGETOWN: The Survey, Recruitment, and Biospecimen Collection Shared Resource at Georgetown University (NIH/NCI) [P30CA051008]
- IWT
- European Regional Development FEDER funds [PI15/00059, PI16/01292, CB-161200301]
- Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]
- Netherlands Organisation of Scientific Research grant [NWO 91109024]
- Pink Ribbon grants [110005, 2014-187.WO76]
- BBMRI [NWO 184.021.007/CP46]
- Transcan grant JTC 2012 Cancer [12-054]
- National Institute of Health [1R 03CA130065]
- HUNBOCS: Hungarian Research Grants [KTIA-OTKA CK-80745, NKFI_OTKA K-112228, TUDFO/51757/2019-ITM]
- Carlos III National Health Institute - FEDER funds-a way to build Europe [PI16/00563, PI19/00553]
- Carlos III National Health Institute - FEDER funds-a way to build Europe (CIBERONC)
- Government of Catalonia (Pla estrategic de recerca i innovacio en salut (PERIS) Project MedPerCan) [2017SGR1282, 2017SGR496]
- CERCA program
- INHERIT: Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program [CRN-87521]
- Ministry of Economic Development, Innovation and Export Trade-grant [PSR-SIIRI-701]
- 5x1000 Istituto Oncologico Veneto grant
- National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea [HI16C1127, 1020350, 1420190]
- KUMC: NIGMS [P20 GM130423]
- MAYO: NIH [CA116167, CA192393, CA176785]
- NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- European Union Seventh Framework Program (2007Y2013)/European Research Council [310018]
- MODSQUAD: MH CZ-DRO (MMCI) [00209805, LM2018125]
- MEYS-NPS [I-LO1413]
- Charles University in Prague project [UNCE204024]
- Cancer Center Support Grant/Core Grant [P30 CA008748]
- NAROD [1R01 CA149429-01]
- NCI: the Intramural Research Program of the US National Cancer Institute, NIH
- Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-21013-63, N02-CP-65504]
- NNPIO: the Russian Foundation for Basic Research [17-00-00171, 18-515-45012, 19-515-25001]
- NRG Oncology [U10 CA180868]
- NRG SDMC grant [U10 CA180822]
- NRG Administrative Office
- NRG Tissue Bank [CA 27469]
- NRG Statistical and Data Center [CA 37517]
- Fondazione Pisa per la Scienza, project [127/2016]
- Fondazione Pisa, Pisa, Italy [127/16]
- SEABASS: Ministry of Science, Technology and Innovation, Ministry of Higher Education [UM.C/HlR/MOHE/06]
- UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA125183, R01 CA142996, 1U01CA161032]
- Ralph and Marion Falk Medical Research Trust
- Entertainment Industry Fund National Women's Cancer Research Alliance
- American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]
- National Center for Advancing Translational Sciences (NCATS) [UL1TR000124]
- [PBZ_KBN_122/P05/2004]
- [002/RID/2018/19]
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The study found that different PRS313 were associated with contralateral breast cancer risk for BRCA1 and BRCA2 heterozygotes. Adjusting for various factors did not change the association effect sizes. For women with first BC diagnosis < age 40, the 10-year CBC risks for BRCA1 and BRCA2 heterozygotes were 22% and 32%, 13% and 23% respectively.
Purpose To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
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