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Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel.

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Peer-reviewed

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Authors

Levi, Hagai 
Carmi, Shai 
Rosset, Saharon 
Yerushalmi, Rinat 
Zick, Aviad 

Abstract

BACKGROUND: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women. METHODS: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel. RESULTS: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28). CONCLUSIONS: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.

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Peer reviewed: True


Funder: Statistics Netherlands


Funder: Lower Saxonian Cancer Society


Funder: Lise Boserup Fund


Funder: Heidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-Gemeinschaft; FundRef: http://dx.doi.org/10.13039/100018027


Funder: Komen Foundation


Funder: Claudia von Schilling Foundation for Breast Cancer Research


Funder: Ligue Contre le Cancer; FundRef: http://dx.doi.org/10.13039/501100004099


Funder: Sigrid Juselius Foundation


Funder: Kuopion Yliopistollinen Sairaala; FundRef: http://dx.doi.org/10.13039/501100004092


Funder: Sheffield Experimental Cancer Medicine Centre


Funder: Stockholm läns landsting; FundRef: http://dx.doi.org/10.13039/501100011727


Funder: Department of Health and Human Services (USA)


Funder: Stichting Tegen Kanker; FundRef: http://dx.doi.org/10.13039/501100005026


Funder: David F. and Margaret T. Grohne Family Foundation; FundRef: http://dx.doi.org/10.13039/100009769


Funder: Sundhed og Sygdom, Det Frie Forskningsråd; FundRef: http://dx.doi.org/10.13039/100008392


Funder: Stavros Niarchos Foundation


Funder: Institute of the Ruhr University Bochum


Funder: Institute of Cancer Research; FundRef: http://dx.doi.org/10.13039/501100000027


Funder: Fondation du cancer du sein du Québec; FundRef: http://dx.doi.org/10.13039/100016328


Funder: Institut National de la Santé et de la Recherche Médicale; FundRef: http://dx.doi.org/10.13039/501100001677


Funder: Institute for Prevention and Occupational Medicine


Funder: K.G. Jebsen Centre for Breast Cancer Research


Funder: Research Centre for Genetic Engineering and Biotechnology


Funder: Robert and Kate Niehaus Clinical Cancer Genetics Initiative


Funder: Rudolf Bartling Foundation


Funder: Karolinska Institutet; FundRef: http://dx.doi.org/10.13039/501100004047


Funder: Robert Bosch Stiftung; FundRef: http://dx.doi.org/10.13039/501100001646


Funder: Intramural Research Funds of the National Cancer Institute (USA)


Funder: Intramural Research Program of the Division of Cancer Epidemiology and Genetics


Funder: Centre International de Recherche sur le Cancer; FundRef: http://dx.doi.org/10.13039/100008700


Funder: Queensland Cancer Fund


Funder: Red Temática de Investigación Cooperativa en Cáncer


Funder: Intramural Research Program of the National Institutes of Health


Funder: National Health Service (UK)


Funder: Ministerie van Volksgezondheid, Welzijn en Sport; FundRef: http://dx.doi.org/10.13039/501100002999


Funder: Märit and Hans Rausings Initiative Against Breast Cancer


Funder: Associazione Italiana per la Ricerca sul Cancro; FundRef: http://dx.doi.org/10.13039/501100005010


Funder: Fundación Científica Asociación Española Contra el Cáncer; FundRef: http://dx.doi.org/10.13039/501100002704


Funder: Agence Nationale de la Recherche; FundRef: http://dx.doi.org/10.13039/501100001665


Funder: Dutch Prevention Funds,


Funder: Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail


Funder: American Cancer Society; FundRef: http://dx.doi.org/10.13039/100000048


Funder: Dutch Zorg Onderzoek


Funder: Alexander von Humboldt-Stiftung; FundRef: http://dx.doi.org/10.13039/100005156


Funder: Ministerio de Economia y Competitividad (Spain)


Funder: Against Breast Cancer; FundRef: http://dx.doi.org/10.13039/100013129


Funder: Mutuelle Générale de l’Education Nationale


Funder: Dietmar-Hopp Foundation,


Funder: Division of Cancer Prevention, National Cancer Institute; FundRef: http://dx.doi.org/10.13039/100007316


Funder: World Cancer Research Fund; FundRef: http://dx.doi.org/10.13039/501100000321


Funder: Genome Québec


Funder: National Cancer Research Network


Funder: Berta Kamprad Foundation FBKS


Funder: Biomedical Research Centre at Guy’s and St Thomas


Funder: Genome Canada; FundRef: http://dx.doi.org/10.13039/100008762


Funder: Friends of Hannover Medical School


Funder: Breast Cancer Research Foundation; FundRef: http://dx.doi.org/10.13039/100001006


Funder: Breast Cancer Now


Funder: UK National Institute for Health Research Biomedical Research Centre


Funder: University of Crete; FundRef: http://dx.doi.org/10.13039/501100004429


Funder: National Breast Cancer Foundation (Finland)


Funder: European Regional Development Fund; FundRef: http://dx.doi.org/10.13039/501100008530


Funder: National Breast Cancer Foundation (Australia)


Funder: Directorate-General XII, Science, Research, and Development; FundRef: http://dx.doi.org/10.13039/501100012517


Funder: Baden Württemberg Ministry of Science, Research and Arts


Funder: VicHealth; FundRef: http://dx.doi.org/10.13039/501100001231


Funder: Victorian Breast Cancer Research Consortium.


Funder: Finnish Cancer Foundation


Funder: Fomento de la Investigación Clínica Independiente


Funder: the Cancer Biology Research Center (CBRC), Djerassi Oncology Center


Funder: Tel Aviv University Center for AI and Data Science


Funder: University of Oulu


Funder: National Breast Cancer Foundation (JS)


Funder: Safra Center for Bioinformatics


Funder: Fondation de France, Institut National du Cancer


Funder: University of Utah; FundRef: http://dx.doi.org/10.13039/100007747


Funder: National Cancer Center Research and Development Fund (Japan)


Funder: Oak Foundation; FundRef: http://dx.doi.org/10.13039/100001275


Funder: New South Wales Cancer Council


Funder: North Carolina University Cancer Research Fund


Funder: Kreftforeningen; FundRef: http://dx.doi.org/10.13039/100008730


Funder: Northern California Breast Cancer Family Registry


Funder: Institut Gustave Roussy


Funder: Huntsman Cancer Institute, University of Utah; FundRef: http://dx.doi.org/10.13039/100010638


Funder: Ovarian Cancer Research Fund; FundRef: http://dx.doi.org/10.13039/100001282


Funder: NIHR Oxford Biomedical Research Centre; FundRef: http://dx.doi.org/10.13039/501100013373


Funder: Hellenic Health Foundation; FundRef: http://dx.doi.org/10.13039/501100018706


Funder: Oulun Yliopistollinen Sairaala; FundRef: http://dx.doi.org/10.13039/501100018949


Funder: Helmholtz Society


Funder: Herlev and Gentofte Hospital


Funder: PSRSIIRI-701


Funder: Helsinki University Hospital Research Fund


Funder: Cancer Council Victoria; FundRef: http://dx.doi.org/10.13039/501100000951


Funder: National Research Council (Italy)


Funder: Cancer Council Tasmania; FundRef: http://dx.doi.org/10.13039/501100001169


Funder: Cancer Council Western Australia; FundRef: http://dx.doi.org/10.13039/501100001170


Funder: Hamburger Krebsgesellschaft; FundRef: http://dx.doi.org/10.13039/100018515


Funder: Gustav V Jubilee foundation


Funder: National Program of Cancer Registries


Funder: Cancer Council South Australia; FundRef: http://dx.doi.org/10.13039/501100000950


Funder: Cancer Council NSW; FundRef: http://dx.doi.org/10.13039/501100001102


Funder: Guy's & St. Thomas' NHS Foundation Trust


Funder: Cancer Institute NSW; FundRef: http://dx.doi.org/10.13039/501100001171


Funder: Cancer Foundation of Western Australia


Funder: Netherlands Cancer Registry (NKR),


Funder: Cancer Fund of North Savo

Keywords

Genomics, Polymorphism, Genetic, Humans, Female, Breast Neoplasms, Genome-Wide Association Study, Jews, Israel, Genetic Predisposition to Disease, Risk Factors, Multifactorial Inheritance, Transcription Factors

Journal Title

J Med Genet

Conference Name

Journal ISSN

0022-2593
1468-6244

Volume Title

Publisher

BMJ
Sponsorship
Medical Research Council (G1000143)
National Cancer Institute (U19CA148537)
European Commission (223175)
National Cancer Institute (R01CA128978)
National Cancer Institute (U19CA148065)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Wellcome Trust (203477/Z/16/Z)
Cancer Research UK (A10710)
Cancer Research UK (A16563)
Cancer Research UK (A12014)
Cancer Research UK (A10118)
National Cancer Institute (P30CA023100)