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

Levi H, Carmi S, Rosset S, Yerushalmi R, Zick A, Yablonski-Peretz T, Wang Q, Bolla MK, Dennis J, Michailidou K, Lush M, Ahearn T, Andrulis IL, Anton-Culver H, Antoniou AC, Arndt V, Augustinsson A, Auvinen P, Freeman LB, Beckmann M, Behrens S, Bermisheva M, Bodelon C, Bogdanova NV, Bojesen SE, Brenner H, Byers H, Camp N, Castelao J, Chang-Claude J, Chirlaque MD, Chung W, Clarke C, Collee MJ, Colonna S, Couch F, Cox A, Cross SS, Czene K, Daly M, Devilee P, Dork T, Dossus L, Eccles DM, Eliassen AH, Eriksson M, Evans G, Fasching P, Fletcher O, Flyger H, Fritschi L, Gabrielson M, Gago-Dominguez M, García-Closas M, Garcia-Saenz JA, Genkinger J, Giles GG, Goldberg M, Guénel P, Hall P, Hamann U, He W, Hillemanns P, Hollestelle A, Hoppe R, Hopper J, Jakovchevska S, Jakubowska A, Jernström H, John E, Johnson N, Jones M, Vijai J, Kaaks R, Khusnutdinova E, Kitahara C, Koutros S, Kristensen V, Kurian AW, Lacey J, Lambrechts D, Le Marchand L, Lejbkowicz F, Lindblom A, Loibl S, Lori A, Lubinski J, Mannermaa A, Manoochehri M, Mavroudis D, Menon U, Mulligan AM, Murphy R, Nevelsteen I, Newman WG, Obi N, O’Brien K, Offit K, Olshan A, Plaseska-Karanfilska D, Olson J, Panico S, Park-Simon TW, Patel A, Peterlongo P, Rack B, Radice P, Rennert G, Rhenius V, Romero A, Saloustros E, Sandler D, Schmidt MK, Schwentner L, Shah M, Sharma P, Simard J, Southey M, Stone J, Tapper WJ, Taylor J, Teras L, Toland AE, Troester M, Truong T, van der Kolk LE, Weinberg C, Wendt C, Yang XR, Zheng W, Ziogas A, Dunning AM, Pharoah P, Easton DF, Ben-Sachar S, Elefant N, Shamir R, Elkon R (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Article Number: jmg-2023-109185

DOI: 10.1136/jmg-2023-109185

Abstract

To date, most BC GWASs have been performed Background Polygenic risk score (PRS), calculated in individuals of European (EUR) ancestry, and based on genome-wide association studies (GWASs), the generalisation of EUR-based PRS to other can improve breast cancer (BC) risk assessment. 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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Involved external institutions

University of California Irvine United States (USA) (US) Université Laval (UL) Canada (CA) Tel Aviv University Israel (IL) Hebrew University of Jerusalem Israel (IL) Rabin Medical Center / מרכז רפואי רבין‎‎ Israel (IL) Hadassah Medical Center / מרכז רפואי הדסה‎‎ Israel (IL) University of Cambridge United Kingdom (GB) National Cancer Institute (NCI) United States (USA) (US) Mount Sinai Hospital (MSH) Canada (CA) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Lund University / Lunds universitet Sweden (SE) University of Eastern Finland Finland (FI) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) American Cancer Society United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Gentofte Hospital Denmark (DK) Health Innovation Manchester United Kingdom (GB) University of Utah United States (USA) (US) Instituto de Investigación Sanitaria Galicia Sur Spain (ES) Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBER-ESP) Spain (ES) Columbia University United States (USA) (US) University of Sydney (USYD) Australia (AU) Erasmus University Medical Center (MC) Netherlands (NL) Mayo Clinic United States (USA) (US) University of Sheffield United Kingdom (GB) Karolinska Institute Sweden (SE) Fox Chase Cancer Center United States (USA) (US) Leiden University Medical Center Netherlands (NL) University of Southampton United Kingdom (GB) The Institute of Cancer Research (ICR) United Kingdom (GB) Curtin University Australia (AU) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) Hospital Clínico San Carlos Spain (ES) Cancer Council Victoria Australia (AU) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie Germany (DE) Melbourne School of Population and Global Health Australia (AU) Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov" (RCGEB) Republic of North Macedonia (MK) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Stanford University United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) City of Hope Medical Center United States (USA) (US) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) University of Hawaii (U.H.) United States (USA) (US) Clalit Health Services Israel (IL) GBG Forschungs GmbH (German Breast Group) Germany (DE) University General Hospital of Heraklion Greece (GR) University College London (UCL) United Kingdom (GB) University of Toronto Canada (CA) University of British Columbia Canada (CA) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) National Institute of Environmental Health Sciences (NIEHS) United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) Università degli Studi di Napoli Federico II Italy (IT) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Universitätsklinikum Ulm Germany (DE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) General University Hospital of Larissa Greece (GR) Netherlands Cancer Institute (NKI) Netherlands (NL) University of Kansas Medical Center United States (USA) (US) Ohio State University United States (USA) (US) Vanderbilt University Medical Center United States (USA) (US)

How to cite

APA:

Levi, H., Carmi, S., Rosset, S., Yerushalmi, R., Zick, A., Yablonski-Peretz, T.,... Elkon, R. (2023). Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel. Journal of Medical Genetics. https://doi.org/10.1136/jmg-2023-109185

MLA:

Levi, Hagai, et al. "Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel." Journal of Medical Genetics (2023).

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