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

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


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.


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:

Funder: Komen Foundation

Funder: Claudia von Schilling Foundation for Breast Cancer Research

Funder: Ligue Contre le Cancer; FundRef:

Funder: Sigrid Juselius Foundation

Funder: Kuopion Yliopistollinen Sairaala; FundRef:

Funder: Sheffield Experimental Cancer Medicine Centre

Funder: Stockholm läns landsting; FundRef:

Funder: Department of Health and Human Services (USA)

Funder: Stichting Tegen Kanker; FundRef:

Funder: David F. and Margaret T. Grohne Family Foundation; FundRef:

Funder: Sundhed og Sygdom, Det Frie Forskningsråd; FundRef:

Funder: Stavros Niarchos Foundation

Funder: Institute of the Ruhr University Bochum

Funder: Institute of Cancer Research; FundRef:

Funder: Fondation du cancer du sein du Québec; FundRef:

Funder: Institut National de la Santé et de la Recherche Médicale; FundRef:

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:

Funder: Robert Bosch Stiftung; FundRef:

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:

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:

Funder: Märit and Hans Rausings Initiative Against Breast Cancer

Funder: Associazione Italiana per la Ricerca sul Cancro; FundRef:

Funder: Fundación Científica Asociación Española Contra el Cáncer; FundRef:

Funder: Agence Nationale de la Recherche; FundRef:

Funder: Dutch Prevention Funds,

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

Funder: American Cancer Society; FundRef:

Funder: Dutch Zorg Onderzoek

Funder: Alexander von Humboldt-Stiftung; FundRef:

Funder: Ministerio de Economia y Competitividad (Spain)

Funder: Against Breast Cancer; FundRef:

Funder: Mutuelle Générale de l’Education Nationale

Funder: Dietmar-Hopp Foundation,

Funder: Division of Cancer Prevention, National Cancer Institute; FundRef:

Funder: World Cancer Research Fund; FundRef:

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:

Funder: Friends of Hannover Medical School

Funder: Breast Cancer Research Foundation; FundRef:

Funder: Breast Cancer Now

Funder: UK National Institute for Health Research Biomedical Research Centre

Funder: University of Crete; FundRef:

Funder: National Breast Cancer Foundation (Finland)

Funder: European Regional Development Fund; FundRef:

Funder: National Breast Cancer Foundation (Australia)

Funder: Directorate-General XII, Science, Research, and Development; FundRef:

Funder: Baden Württemberg Ministry of Science, Research and Arts

Funder: VicHealth; FundRef:

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:

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

Funder: Oak Foundation; FundRef:

Funder: New South Wales Cancer Council

Funder: North Carolina University Cancer Research Fund

Funder: Kreftforeningen; FundRef:

Funder: Northern California Breast Cancer Family Registry

Funder: Institut Gustave Roussy

Funder: Huntsman Cancer Institute, University of Utah; FundRef:

Funder: Ovarian Cancer Research Fund; FundRef:

Funder: NIHR Oxford Biomedical Research Centre; FundRef:

Funder: Hellenic Health Foundation; FundRef:

Funder: Oulun Yliopistollinen Sairaala; FundRef:

Funder: Helmholtz Society

Funder: Herlev and Gentofte Hospital

Funder: PSRSIIRI-701

Funder: Helsinki University Hospital Research Fund

Funder: Cancer Council Victoria; FundRef:

Funder: National Research Council (Italy)

Funder: Cancer Council Tasmania; FundRef:

Funder: Cancer Council Western Australia; FundRef:

Funder: Hamburger Krebsgesellschaft; FundRef:

Funder: Gustav V Jubilee foundation

Funder: National Program of Cancer Registries

Funder: Cancer Council South Australia; FundRef:

Funder: Cancer Council NSW; FundRef:

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

Funder: Cancer Institute NSW; FundRef:

Funder: Cancer Foundation of Western Australia

Funder: Netherlands Cancer Registry (NKR),

Funder: Cancer Fund of North Savo


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

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J Med Genet

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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)