Thumbnail Image
Item

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction

Yiangou, K.
; 
Mavaddat, N.
; 
Dennis, J.
; 
Zanti, M.
; 
Wang, Q.
; 
Bolla, M. K.
; 
Abubakar, M.
; 
Ahearn, T. U.
; 
Andrulis, I. L.
; 
Anton-Culver, H.
... show 10 more
Citations
Google Scholar:
Lookup
Altmetric:
Abstract
BACKGROUND: The 313-variant polygenic risk score (PRS(313)) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS(313) across different European populations which could influence risk estimation has not been performed. METHODS: We explored the distribution of PRS(313) 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 PRS(313) differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS(313) 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.
Authors
Yiangou, K.
Mavaddat, N.
Dennis, J.
Zanti, M.
Wang, Q.
Bolla, M. K.
Abubakar, M.
Ahearn, T. U.
Andrulis, I. L.
Anton-Culver, H.
Antonenkova, N. N.
Arndt, V.
Aronson, K. J.
Augustinsson, A.
Baten, A.
Behrens, S.
Bermisheva, M.
Berrington de Gonzalez, A.
Białkowska, K.
Boddicker, N.
Bodelon, C.
Bogdanova, N. V.
Bojesen, S. E.
Brantley, K. D.
Brauch, H.
Brenner, H.
Camp, N. J.
Canzian, F.
Castelao, J. E.
Cessna, M. H.
Chang-Claude, J.
Chenevix-Trench, G.
Chung, W. K.
Colonna, S. V.
Couch, F. J.
Cox, A.
Cross, S. S.
Czene, K.
Daly, M. B.
Devilee, P.
Dörk, T.
Dunning, A. M.
Eccles, D. M.
Eliassen, A. H.
Engel, C.
Eriksson, M.
Evans, D. G.
Fasching, P. A.
Fletcher, O.
Flyger, H.
Fritschi, L.
Gago-Dominguez, M.
Gentry-Maharaj, A.
González-Neira, A.
Guénel, P.
Hahnen, E.
Haiman, C. A.
Hamann, U.
Hartikainen, J. M.
Ho, V.
Hodge, J.
Hollestelle, A.
Honisch, E.
Hooning, M. J.
Hoppe, R.
Hopper, J. L.
Howell, S.
Howell, A.
Jakovchevska, S.
Jakubowska, A.
Jernström, H.
Johnson, N.
Kaaks, R.
Khusnutdinova, E. K.
Kitahara, C. M.
Koutros, S.
Kristensen, V. N.
Lacey, J. V.
Lambrechts, D.
Lejbkowicz, F.
Lindblom, A.
Lush, M.
Mannermaa, A.
Mavroudis, D.
Menon, U.
Murphy, R. A.
Nevanlinna, H.
Obi, N.
Offit, K.
Park-Simon, T. W.
Patel, A. V.
Peng, C.
Peterlongo, P.
Pita, G.
Plaseska-Karanfilska, D.
Pylkäs, K.
Radice, P.
Rashid, M. U.
Rennert, G.
Roberts, E.
Rodriguez, J.
Romero, A.
Rosenberg, E. H.
Saloustros, E.
Sandler, D. P.
Sawyer, E. J.
Schmutzler, R. K.
Scott, C. G.
Shu, X. O.
Southey, M. C.
Stone, J.
Taylor, J. A.
Teras, L. R.
van de Beek, I.
Willett, W.
Winqvist, R.
Zheng, W.
Vachon, C. M.
Schmidt, M. K.
Hall, P.
MacInnis, R. J.
Milne, R. L.
Pharoah, P. D. P.
Simard, J.
Antoniou, A. C.
Easton, D. F.
Michailidou, K.
Affiliation
Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus. Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, 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, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA. NN Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, ON, Canada. Oncology, Clinical Sciences in Lund, Lund University, Lund, Sweden. Department of Oncology, Leuven Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Institute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia. Petersburg State University, St. Petersburg, Russia. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. Department of Population Science, American Cancer Society, Atlanta, GA, USA. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany. Gynaecology Research Unit, Hannover Medical School, Hannover, Germany. Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. iFIT-Cluster of Excellence, University of Tübingen, Tübingen, Germany. German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tübingen, Tübingen, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur-Vigo-Spain, Vigo, Spain. Department of Pathology, Intermountain Healthcare, Salt Lake City, UT, USA. Intermountain Biorepository, Intermountain Healthcare, Salt Lake City, UT, USA. Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK. Division of Neuroscience, School of Medicine and Population Health, 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, The Netherlands. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. 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. Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany. Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. 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 Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany. 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, WA, Australia. Cancer Genetics and Epidemiology Group, Genomic Medicine Group, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain. MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK. Department of Women's Cancer, Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK. Human Genotyping Unit-CeGen, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Spanish Network on Rare Diseases (CIBERER), Madrid, Spain. Team 'Exposome and Heredity', CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ, Villejuif, France. Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. Cancer RC, University of Eastern Finland, Kuopio, Finland. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland. Health Innovation and Evaluation Hub, Université de Montréal Hospital Research Centre (CRCHUM), Montréal, QC, Canada. Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD, Rotterdam, The Netherlands. Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. University of Tübingen, Tübingen, Germany. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Nightingale/Prevent Breast Cancer Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. Manchester Breast Centre, Manchester Cancer Research Centre, The Christie Hospital, Manchester, UK. Division of Cancer Sciences, University of Manchester, Manchester, UK. Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', MASA, Skopje, Republic of North Macedonia. Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland. Department of Genetics and Fundamental Medicine, Ufa University of Science and Technology, Ufa, Russia. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway. Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA. City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA, USA. Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium. VIB Center for Cancer Biology, VIB, Leuven, Belgium. Carmel Medical Center, Haifa, Israel. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland. Biobank of Eastern Finland, Kuopio University Hospital, Kuopio, Finland. Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada. Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Institute for Occupational and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Genome Diagnostics Program, IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy. Laboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland. Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland. Unit of Predictive Medicine, Molecular Bases of Genetic Risk, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori (INT), Milan, Italy. Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan. Technion, Faculty of Medicine and Association for Promotion of Research in Precision Medicine, Haifa, Israel. Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain. Department of Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Department of Oncology, University Hospital of Larissa, Larissa, Greece. Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. School of Cancer and Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London, UK. Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia. Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia. Genetic Epidemiology Group, School of Population and Global Health, University of Western Australia, Perth, WA, Australia. Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. Department of Clinical Genetics, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. Department of Oncology, Södersjukhuset, Stockholm, Sweden. Department of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, CA, USA. Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Québec City, QC, Canada. Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus. kyriakimi@cing.ac.cy. Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. kyriakimi@cing.ac.cy.
Description
Date
2024
Publisher
Collections
All Christie Publications
Show all metadata
Files
Thumbnail Image
Found from Unpaywall
Adobe PDF, 1.2 MB
Keywords
Type
Article
Citation
Yiangou K, Mavaddat N, Dennis J, Zanti M, Wang Q, Bolla MK, et al. Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction. Breast cancer research : BCR. 2024 Dec 29;26(1):189. PubMed PMID: 39734228. Pubmed Central PMCID: PMC11682615. Epub 2024/12/30. eng.
Journal Title
Journal ISSN
Volume Title
URI
https://christie.openrepository.com/handle/10541/627995
Embedded videos