Breast Cancer Research (Dec 2024)
Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction
- Kristia Yiangou,
- Nasim Mavaddat,
- Joe Dennis,
- Maria Zanti,
- Qin Wang,
- Manjeet K. Bolla,
- Mustapha Abubakar,
- Thomas U. Ahearn,
- Irene L. Andrulis,
- Hoda Anton-Culver,
- Natalia N. Antonenkova,
- Volker Arndt,
- Kristan J. Aronson,
- Annelie Augustinsson,
- Adinda Baten,
- Sabine Behrens,
- Marina Bermisheva,
- Amy Berrington de Gonzalez,
- Katarzyna Białkowska,
- Nicholas Boddicker,
- Clara Bodelon,
- Natalia V. Bogdanova,
- Stig E. Bojesen,
- Kristen D. Brantley,
- Hiltrud Brauch,
- Hermann Brenner,
- Nicola J. Camp,
- Federico Canzian,
- Jose E. Castelao,
- Melissa H. Cessna,
- Jenny Chang-Claude,
- Georgia Chenevix-Trench,
- Wendy K. Chung,
- NBCS Collaborators,
- Sarah V. Colonna,
- Fergus J. Couch,
- Angela Cox,
- Simon S. Cross,
- Kamila Czene,
- Mary B. Daly,
- Peter Devilee,
- Thilo Dörk,
- Alison M. Dunning,
- Diana M. Eccles,
- A. Heather Eliassen,
- Christoph Engel,
- Mikael Eriksson,
- D. Gareth Evans,
- Peter A. Fasching,
- Olivia Fletcher,
- Henrik Flyger,
- Lin Fritschi,
- Manuela Gago-Dominguez,
- Aleksandra Gentry-Maharaj,
- Anna González-Neira,
- Pascal Guénel,
- Eric Hahnen,
- Christopher A. Haiman,
- Ute Hamann,
- Jaana M. Hartikainen,
- Vikki Ho,
- James Hodge,
- Antoinette Hollestelle,
- Ellen Honisch,
- Maartje J. Hooning,
- Reiner Hoppe,
- John L. Hopper,
- Sacha Howell,
- Anthony Howell,
- ABCTB Investigators,
- kConFab Investigators,
- Simona Jakovchevska,
- Anna Jakubowska,
- Helena Jernström,
- Nichola Johnson,
- Rudolf Kaaks,
- Elza K. Khusnutdinova,
- Cari M. Kitahara,
- Stella Koutros,
- Vessela N. Kristensen,
- James V. Lacey,
- Diether Lambrechts,
- Flavio Lejbkowicz,
- Annika Lindblom,
- Michael Lush,
- Arto Mannermaa,
- Dimitrios Mavroudis,
- Usha Menon,
- Rachel A. Murphy,
- Heli Nevanlinna,
- Nadia Obi,
- Kenneth Offit,
- Tjoung-Won Park-Simon,
- Alpa V. Patel,
- Cheng Peng,
- Paolo Peterlongo,
- Guillermo Pita,
- Dijana Plaseska-Karanfilska,
- Katri Pylkäs,
- Paolo Radice,
- Muhammad U. Rashid,
- Gad Rennert,
- Eleanor Roberts,
- Juan Rodriguez,
- Atocha Romero,
- Efraim H. Rosenberg,
- Emmanouil Saloustros,
- Dale P. Sandler,
- Elinor J. Sawyer,
- Rita K. Schmutzler,
- Christopher G. Scott,
- Xiao-Ou Shu,
- Melissa C. Southey,
- Jennifer Stone,
- Jack A. Taylor,
- Lauren R. Teras,
- Irma van de Beek,
- Walter Willett,
- Robert Winqvist,
- Wei Zheng,
- Celine M. Vachon,
- Marjanka K. Schmidt,
- Per Hall,
- Robert J. MacInnis,
- Roger L. Milne,
- Paul D. P. Pharoah,
- Jacques Simard,
- Antonis C. Antoniou,
- Douglas F. Easton,
- Kyriaki Michailidou
Affiliations
- Kristia Yiangou
- Biostatistics Unit, The Cyprus Institute of Neurology and Genetics
- Nasim Mavaddat
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Joe Dennis
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Maria Zanti
- Biostatistics Unit, The Cyprus Institute of Neurology and Genetics
- Qin Wang
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Manjeet K. Bolla
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Mustapha Abubakar
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Thomas U. Ahearn
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Irene L. Andrulis
- Fred A, Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
- Hoda Anton-Culver
- Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine
- Natalia N. Antonenkova
- NN Alexandrov Research Institute of Oncology and Medical Radiology
- Volker Arndt
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Kristan J. Aronson
- Department of Public Health Sciences, and Cancer Research Institute, Queen’s University
- Annelie Augustinsson
- Oncology, Clinical Sciences in Lund, Lund University
- Adinda Baten
- Department of Oncology, Leuven Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven
- Sabine Behrens
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Marina Bermisheva
- Institute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences
- Amy Berrington de Gonzalez
- Division of Genetics and Epidemiology, The Institute of Cancer Research
- Katarzyna Białkowska
- Department of Genetics and Pathology, Pomeranian Medical University
- Nicholas Boddicker
- Department of Quantitative Health Sciences, Mayo Clinic
- Clara Bodelon
- Department of Population Science, American Cancer Society
- Natalia V. Bogdanova
- NN Alexandrov Research Institute of Oncology and Medical Radiology
- Stig E. Bojesen
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Kristen D. Brantley
- Department of Epidemiology, Harvard TH Chan School of Public Health
- Hiltrud Brauch
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Nicola J. Camp
- Department of Internal Medicine and Huntsman Cancer Institute, University of Utah
- Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ)
- Jose E. Castelao
- Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur-Vigo-Spain
- Melissa H. Cessna
- Department of Pathology, Intermountain Healthcare
- Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Georgia Chenevix-Trench
- Cancer Research Program, QIMR Berghofer Medical Research Institute
- Wendy K. Chung
- Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School
- NBCS Collaborators
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet
- Sarah V. Colonna
- Department of Internal Medicine and Huntsman Cancer Institute, University of Utah
- Fergus J. Couch
- Department of Laboratory Medicine and Pathology, Mayo Clinic
- Angela Cox
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield
- Simon S. Cross
- Division of Neuroscience, School of Medicine and Population Health, University of Sheffield
- Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Mary B. Daly
- Department of Clinical Genetics, Fox Chase Cancer Center
- Peter Devilee
- Department of Pathology, Leiden University Medical Center
- Thilo Dörk
- Gynaecology Research Unit, Hannover Medical School
- Alison M. Dunning
- Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Diana M. Eccles
- Faculty of Medicine, University of Southampton
- A. Heather Eliassen
- Department of Epidemiology, Harvard TH Chan School of Public Health
- Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig
- Mikael Eriksson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- D. Gareth Evans
- Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre
- Peter A. Fasching
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen
- Olivia Fletcher
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Henrik Flyger
- Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Lin Fritschi
- School of Population Health, Curtin University
- Manuela Gago-Dominguez
- Cancer Genetics and Epidemiology Group, Genomic Medicine Group, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Complejo Hospitalario Universitario de Santiago, SERGAS
- Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London
- Anna González-Neira
- Human Genotyping Unit-CeGen, Spanish National Cancer Research Centre (CNIO)
- Pascal Guénel
- Team ‘Exposome and Heredity’, CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ
- Eric Hahnen
- Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne
- Christopher A. Haiman
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California
- Ute Hamann
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)
- Jaana M. Hartikainen
- Cancer RC, University of Eastern Finland
- Vikki Ho
- Health Innovation and Evaluation Hub, Université de Montréal Hospital Research Centre (CRCHUM)
- James Hodge
- Department of Population Science, American Cancer Society
- Antoinette Hollestelle
- Department of Medical Oncology, Erasmus MC Cancer Institute
- Ellen Honisch
- Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf
- Maartje J. Hooning
- Department of Medical Oncology, Erasmus MC Cancer Institute
- Reiner Hoppe
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
- John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Sacha Howell
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre
- Anthony Howell
- Division of Cancer Sciences, University of Manchester
- ABCTB Investigators
- Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, University of Sydney
- kConFab Investigators
- Research Department, Peter MacCallum Cancer Center
- Simona Jakovchevska
- Research Centre for Genetic Engineering and Biotechnology ‘Georgi D. Efremov’, MASA
- Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University
- Helena Jernström
- Oncology, Clinical Sciences in Lund, Lund University
- Nichola Johnson
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Elza K. Khusnutdinova
- Institute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences
- Cari M. Kitahara
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH
- Stella Koutros
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Vessela N. Kristensen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
- James V. Lacey
- Department of Computational and Quantitative Medicine, City of Hope
- Diether Lambrechts
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
- Flavio Lejbkowicz
- Carmel Medical Center
- Annika Lindblom
- Department of Molecular Medicine and Surgery, Karolinska Institutet
- Michael Lush
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Arto Mannermaa
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland
- Dimitrios Mavroudis
- Department of Medical Oncology, University Hospital of Heraklion
- Usha Menon
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London
- Rachel A. Murphy
- School of Population and Public Health, University of British Columbia
- Heli Nevanlinna
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki
- Nadia Obi
- Institute for Occupational and Maritime Medicine, University Medical Center Hamburg-Eppendorf
- Kenneth Offit
- Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center
- Tjoung-Won Park-Simon
- Gynaecology Research Unit, Hannover Medical School
- Alpa V. Patel
- Department of Population Science, American Cancer Society
- Cheng Peng
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
- Paolo Peterlongo
- Genome Diagnostics Program, IFOM ETS - The AIRC Institute of Molecular Oncology
- Guillermo Pita
- Human Genotyping Unit-CeGen, Spanish National Cancer Research Centre (CNIO)
- Dijana Plaseska-Karanfilska
- Research Centre for Genetic Engineering and Biotechnology ‘Georgi D. Efremov’, MASA
- Katri Pylkäs
- Laboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, Biocenter Oulu, University of Oulu
- Paolo Radice
- Unit of Predictive Medicine, Molecular Bases of Genetic Risk, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori (INT)
- Muhammad U. Rashid
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)
- Gad Rennert
- Technion, Faculty of Medicine and Association for Promotion of Research in Precision Medicine
- Eleanor Roberts
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre
- Juan Rodriguez
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Atocha Romero
- Medical Oncology Department, Hospital Universitario Puerta de Hierro
- Efraim H. Rosenberg
- Department of Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital
- Emmanouil Saloustros
- Department of Oncology, University Hospital of Larissa
- Dale P. Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH
- Elinor J. Sawyer
- School of Cancer and Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy’s Campus, King’s College London
- Rita K. Schmutzler
- Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne
- Christopher G. Scott
- Department of Quantitative Health Sciences, Mayo Clinic
- Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
- Melissa C. Southey
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University
- Jennifer Stone
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Jack A. Taylor
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH
- Lauren R. Teras
- Department of Population Science, American Cancer Society
- Irma van de Beek
- Department of Clinical Genetics, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital
- Walter Willett
- Department of Epidemiology, Harvard TH Chan School of Public Health
- Robert Winqvist
- Laboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, Biocenter Oulu, University of Oulu
- Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
- Celine M. Vachon
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic
- Marjanka K. Schmidt
- Division of Molecular Pathology, The Netherlands Cancer Institute
- Per Hall
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Robert J. MacInnis
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Roger L. Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Paul D. P. Pharoah
- Department of Computational Biomedicine, Cedars-Sinai Medical Center
- Jacques Simard
- Genomics Center, Centre Hospitalier Universitaire de Québec – Université Laval Research Center
- Antonis C. Antoniou
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Douglas F. Easton
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Kyriaki Michailidou
- Biostatistics Unit, The Cyprus Institute of Neurology and Genetics
- DOI
- https://doi.org/10.1186/s13058-024-01947-x
- Journal volume & issue
-
Vol. 26,
no. 1
pp. 1 – 14
Abstract
Abstract Background The 313-variant polygenic risk score (PRS313) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed. Methods We explored the distribution of PRS313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction. Results The mean PRS313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment. Conclusions Our results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories.
Keywords
