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

About this Publication
Title
Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel.
Pubmed ID
37451831 (View this publication on the PubMed website)
Digital Object Identifier
Publication
J Med Genet. 2023 Nov 27; Volume 60 (Issue 12): Pages 1186-1197
Authors
Levi H, Carmi S, Rosset S, Yerushalmi R, Zick A, Yablonski-Peretz T, BCAC Consortium, 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, Beane Freeman L, ...show more 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, NBCS Collaborators, Collee MJ, Colonna S, CTS Consortium, 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, ABCTB Investigators, 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 A, 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
Affiliations
  • The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
  • Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
  • Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel.
  • Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
  • Department of oncology, Hadassah Medical Center, Jerusalem, Israel.
  • Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
...show more
  • Oncology, Department of Clinical Sciences in Lund, Lund University, Lund, Sweden.
  • Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
  • Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
  • Department of Population Science, American Cancer Society, Atlanta, GA, USA.
  • Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
  • Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
  • Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt lake city, UT, USA.
  • Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
  • CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
  • Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
  • Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Department of Oncology and Metabolism, Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield, Sheffield, UK.
  • Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
  • Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
  • Gynaecology Research Unit, Hannover Medical School, Hamburg, Germany.
  • Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
  • Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
  • Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • School of Population Health, Curtin University, Perth, Western Australia, Australia.
  • Genomic Medicine Group, International Cancer Genetics and Epidemiology Group, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain.
  • Medical Oncology, Hospital Clinico San Carlos, Madrid, Spain, USA.
  • Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Department of Medicine, McGill University, Montreal, Quebec, Canada.
  • Team 'Exposome and Heredity', CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ, Villejuif, France.
  • Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Medical Oncology, Erasmus Medical Center, Rotterdam, Netherlands.
  • Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Skopje, North Macedonia.
  • Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
  • Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK.
  • Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Institute of Clinical Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA.
  • Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
  • Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • German Breast Group, GmbH, Neu Isenburg, Germany.
  • Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
  • MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College, London, UK.
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
  • Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
  • Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
  • Dipertimento Di Medicina Clinca e Chirurgia, Federico II University, Naples, Italy.
  • Genome Diagnostics Program, IFOM ETS - the AIRC Institute of Molecular Oncology, Milan, Italy.
  • Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
  • Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
  • Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Laboratorio de Oncología Molecular, Hospital Clínico San Carlos, Madrid, Spain.
  • Department of Oncology, University Hospital of Larissa, Larissa, Greece.
  • Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
  • Department of Internal Medicine, Division of Medical Oncology, University of Kansas Medical Center, Westwood, KS, USA.
  • Genomics Center, Molecular Medicine, Université Laval, Quebec, Quebec, Canada.
  • Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
  • Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, Netherlands.
  • Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
  • Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Clalit Research Institute, Clalit Health Services, Ramat Gan, Israel ranel@tauex.tau.ac.il rshamir@tau.ac.il naamael1@clalit.org.il.
  • The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel ranel@tauex.tau.ac.il rshamir@tau.ac.il naamael1@clalit.org.il.
  • Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel ranel@tauex.tau.ac.il rshamir@tau.ac.il naamael1@clalit.org.il.
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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