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Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

Kramer I 1 , Hooning MJ 2 , Mavaddat N 3 , Hauptmann M 4 , Keeman R 1 , Steyerberg EW 5 Show all authors , Giardiello D 6 , Antoniou AC 3 , Pharoah PDP 7 , Canisius S 8 , Abu-Ful Z 9 , Andrulis IL 10 , Anton-Culver H 11 , Aronson KJ 12 , Augustinsson A 13 , Becher H 14 , Beckmann MW 15 , Behrens S 16 , Benitez J 17 , Bermisheva M 18 , Bogdanova NV 19 , Bojesen SE 20 , Bolla MK 3 , Bonanni B 21 , Brauch H 22 , Bremer M 23 , Brucker SY 24 , Burwinkel B 25 , Castelao JE 26 , Chan TL 27 , Chang-Claude J 28 , Chanock SJ 29 , Chenevix-Trench G 30 , Choi JY 31 , Clarke CL 32 , NBCS Collaborators 33 , Collée JM 34 , Couch FJ 35 , Cox A 36 , Cross SS 37 , Czene K 38 , Daly MB 39 , Devilee P 40 , Dörk T 41 , Dos-Santos-Silva I 42 , Dunning AM 43 , Dwek M 44 , Eccles DM 45 , Evans DG 46 , Fasching PA 47 , Flyger H 48 , Gago-Dominguez M 49 , García-Closas M 29 , García-Sáenz JA 50 , Giles GG 51 , Goldgar DE 52 , González-Neira A 53 , Haiman CA 54 , Håkansson N 55 , Hamann U 56 , Hartman M 57 , Heemskerk-Gerritsen BAM 2 , Hollestelle A 2 , Hopper JL 58 , Hou MF 59 , Howell A 60 , ABCTB Investigators 61 , kConFab Investigators 62 , Ito H 63 , Jakimovska M 64 , Jakubowska A 65 , Janni W 66 , John EM 67 , Jung A 16 , Kang D 68 , Kets CM 69 , Khusnutdinova E 70 , Ko YD 71 , Kristensen VN 72 , Kurian AW 73 , Kwong A 74 , Lambrechts D 75 , Le Marchand L 76 , Li J 77 , Lindblom A 78 , Lubiński J 79 , Mannermaa A 80 , Manoochehri M 56 , Margolin S 81 , Matsuo K 63 , Mavroudis D 82 , Meindl A 83 , Milne RL 51 , Mulligan AM 84 , Muranen TA 85 , Neuhausen SL 86 , Nevanlinna H 85 , Newman WG 46 , Olshan AF 87 , Olson JE 88 , Olsson H 13 , Park-Simon TW 41 , Peto J 42 , Petridis C 89 , Plaseska-Karanfilska D 64 , Presneau N 44 , Pylkäs K 90 , Radice P 91 , Rennert G 9 , Romero A 92 , Roylance R 93 , Saloustros E 94 , Sawyer EJ 95 , Schmutzler RK 96 , Schwentner L 66 , Scott C 88 , See MH 97 , Shah M 43 , Shen CY 98 , Shu XO 99 , Siesling S 100 , Slager S 88 , Sohn C 101 , Southey MC 102 , Spinelli JJ 103 , Stone J 104 , Tapper WJ 45 , Tengström M 105 , Teo SH 106 , Terry MB 107 , Tollenaar RAEM 108 , Tomlinson I 109 , Troester MA 87 , Vachon CM 110 , van Ongeval C 111 , van Veen EM 46 , Winqvist R 90 , Wolk A 112 , Zheng W 99 , Ziogas A 11 , Easton DF 7 , Hall P 113 , Schmidt MK 114

Affiliations 

  • 1 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam 1066 CX, the Netherlands
  • 2 Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam 3015 CN, the Netherlands
  • 3 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge CB1 8RN, UK
  • 4 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Epidemiology and Biostatistics, Amsterdam 1066 CX, the Netherlands; Brandenburg Medical School Theodor Fontane, Institute of Biostatistics and Registry Research, Neuruppin 16816, Germany
  • 5 Leiden University Medical Center, Department of Biomedical Data Sciences, Leiden 2333 ZA, the Netherlands; Erasmus MC, Department of Public Health, Rotterdam 3015 GD, the Netherlands
  • 6 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam 1066 CX, the Netherlands; Leiden University Medical Center, Department of Biomedical Data Sciences, Leiden 2333 ZA, the Netherlands
  • 7 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge CB1 8RN, UK; University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge CB1 8RN, UK
  • 8 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam 1066 CX, the Netherlands; The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Carcinogenesis, Amsterdam 1066 CX, the Netherlands
  • 9 Carmel Medical Center and Technion Faculty of Medicine, Clalit National Cancer Control Center, Haifa 35254, Israel
  • 10 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON M5G 1X5, Canada; University of Toronto, Department of Molecular Genetics, Toronto, ON M5S 1A8, Canada
  • 11 University of California Irvine, Department of Epidemiology, Genetic Epidemiology Research Institute, Irvine, CA 92617, USA
  • 12 Queen's University, Department of Public Health Sciences, and Cancer Research Institute, Kingston, ON K7L 3N6, Canada
  • 13 Lund University, Department of Cancer Epidemiology, Clinical Sciences, Lund 222 42, Sweden
  • 14 University Medical Center Hamburg-Eppendorf, Institute of Medical Biometry and Epidemiology, Hamburg 20246, Germany; Charité -Universitätsmedizin Berlin, Institute of Biometry and Clinical Epidemiology, Berlin 10117, Germany
  • 15 University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen 91054, Germany
  • 16 German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg 69120, Germany
  • 17 Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain; Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid 28029, Spain
  • 18 Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa 450054, Russia
  • 19 Hannover Medical School, Department of Radiation Oncology, Hannover 30625, Germany; Hannover Medical School, Gynaecology Research Unit, Hannover 30625, Germany; N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk 223040, Belarus
  • 20 Copenhagen University Hospital, Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev 2730, Denmark; Copenhagen University Hospital, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev 2730, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen 2200, Denmark
  • 21 IEO, European Institute of Oncology IRCCS, Division of Cancer Prevention and Genetics, Milan 20141, Italy
  • 22 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart 70376, Germany; University of Tübingen, iFIT-Cluster of Excellence, Tübingen 72074, Germany; German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Tübingen, Tübingen 72074, Germany
  • 23 Hannover Medical School, Department of Radiation Oncology, Hannover 30625, Germany
  • 24 University of Tübingen, Department of Gynecology and Obstetrics, Tübingen 72076, Germany
  • 25 German Cancer Research Center (DKFZ), Molecular Epidemiology Group, C080, Heidelberg 69120, Germany; University of Heidelberg, Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, Heidelberg 69120, Germany
  • 26 Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Oncology and Genetics Unit, Vigo 36312, Spain
  • 27 Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong; Hong Kong Sanatorium and Hospital, Department of Pathology, Happy Valley, Hong Kong
  • 28 German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg 69120, Germany; University Medical Center Hamburg-Eppendorf, Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), Hamburg 20246, Germany
  • 29 National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20850, USA
  • 30 QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, QLD 4006, Australia
  • 31 Seoul National University Graduate School, Department of Biomedical Sciences, Seoul 03080, Korea; Seoul National University, Cancer Research Institute, Seoul 03080, Korea
  • 32 University of Sydney, Westmead Institute for Medical Research, Sydney, NSW 2145, Australia
  • 33 Oslo University Hospital-Radiumhospitalet, Department of Cancer Genetics, Institute for Cancer Research, Oslo 0379, Norway; University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo 0450, Norway; Vestre Viken Hospital, Department of Research, Drammen 3019, Norway; Oslo University Hospital-Ullevål, Section for Breast and Endocrine Surgery, Department of Cancer, Division of Surgery, Cancer and Transplantation Medicine, Oslo 0450, Norway; Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo 0379, Norway; Akershus University Hospital, Department of Pathology, Lørenskog 1478, Norway; Oslo University Hospital, Department of Tumor Biology, Institute for Cancer Research, Oslo 0379, Norway; Oslo University Hospital-Radiumhospitalet, Department of Oncology, Division of Surgery, Cancer and Transplantation Medicine, Oslo 0379, Norway; Oslo University Hospital-Radiumhospitalet, National Advisory Unit on Late Effects after Cancer Treatment, Department of Oncology, Oslo 0379, Norway; Akershus University Hospital, Department of Oncology, Lørenskog 1478, Norway; Oslo University Hospital, Oslo Breast Cancer Research Consortium, Oslo 0379, Norway; Oslo University Hospital and University of Olso, Department of Medical Genetics, Oslo 0379, Norway
  • 34 Erasmus University Medical Center, Department of Clinical Genetics, Rotterdam 3015 CN, the Netherlands
  • 35 Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN 55905, USA
  • 36 University of Sheffield, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, Sheffield S10 2TN, UK
  • 37 University of Sheffield, Academic Unit of Pathology, Department of Neuroscience, Sheffield S10 2TN, UK
  • 38 Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm 171 65, Sweden
  • 39 Fox Chase Cancer Center, Department of Clinical Genetics, Philadelphia, PA 19111, USA
  • 40 Leiden University Medical Center, Department of Pathology, Leiden 2333 ZA, the Netherlands; Leiden University Medical Center, Department of Human Genetics, Leiden 2333 ZA, the Netherlands
  • 41 Hannover Medical School, Gynaecology Research Unit, Hannover 30625, Germany
  • 42 London School of Hygiene and Tropical Medicine, Department of Non-Communicable Disease Epidemiology, London WC1E 7HT, UK
  • 43 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge CB1 8RN, UK
  • 44 University of Westminster, School of Life Sciences, London W1B 2HW, UK
  • 45 University of Southampton, Faculty of Medicine, Southampton SO17 1BJ, UK
  • 46 University of Manchester, Manchester Academic Health Science Centre, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester M13 9WL, UK; St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, Manchester M13 9WL, UK
  • 47 University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen 91054, Germany; University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, Los Angeles, CA 90095, USA
  • 48 Copenhagen University Hospital, Department of Breast Surgery, Herlev and Gentofte Hospital, Herlev 2730, Denmark
  • 49 Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela 15706, Spain; University of California San Diego, Moores Cancer Center, La Jolla, CA 92037, USA
  • 50 Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Medical Oncology Department, Hospital Clínico San Carlos, Madrid 28040, Spain
  • 51 Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, VIC 3004, Australia; The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, VIC 3010, Australia; Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, Clayton, VIC 3168, Australia
  • 52 Huntsman Cancer Institute, University of Utah School of Medicine, Department of Dermatology, Salt Lake City, UT 84112, USA
  • 53 Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid 28029, Spain
  • 54 University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA 90033, USA
  • 55 Karolinska Institutet, Institute of Environmental Medicine, Stockholm 171 77, Sweden
  • 56 German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg 69120, Germany
  • 57 National University of Singapore and National University Health System, Saw Swee Hock School of Public Health, Singapore 119077, Singapore; National University Health System, Department of Surgery, Singapore 119228, Singapore
  • 58 The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, VIC 3010, Australia
  • 59 Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung 807, Taiwan
  • 60 University of Manchester, Division of Cancer Sciences, Manchester M13 9PL, UK
  • 61 University of Sydney, Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, Sydney, NSW 2145, Australia
  • 62 Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia; The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC 3000, Australia
  • 63 Aichi Cancer Center Research Institute, Division of Cancer Epidemiology and Prevention, Nagoya 464-8681, Japan; Nagoya University Graduate School of Medicine, Division of Cancer Epidemiology, Nagoya 466-8550, Japan
  • 64 MASA, Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Skopje 1000, Republic of North Macedonia
  • 65 Pomeranian Medical University, Department of Genetics and Pathology, Szczecin 71-252, Poland; Pomeranian Medical University, Independent Laboratory of Molecular Biology and Genetic Diagnostics, Szczecin 71-252, Poland
  • 66 University Hospital Ulm, Department of Gynaecology and Obstetrics, Ulm 89075, Germany
  • 67 Stanford Cancer Institute, Stanford University School of Medicine, Department of Epidemiology & Population Health, Stanford, CA 94304, USA
  • 68 Seoul National University Graduate School, Department of Biomedical Sciences, Seoul 03080, Korea; Seoul National University, Cancer Research Institute, Seoul 03080, Korea; Seoul National University College of Medicine, Department of Preventive Medicine, Seoul 03080, Korea
  • 69 the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Clinical Genetics, Amsterdam 1066 CX, the Netherlands
  • 70 Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa 450054, Russia; Bashkir State University, Department of Genetics and Fundamental Medicine, Ufa 450000, Russia
  • 71 Johanniter Krankenhaus, Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Bonn 53177, Germany
  • 72 Oslo University Hospital-Radiumhospitalet, Department of Cancer Genetics, Institute for Cancer Research, Oslo 0379, Norway; Oslo University Hospital and University of Olso, Department of Medical Genetics, Oslo 0379, Norway
  • 73 Stanford Cancer Institute, Stanford University School of Medicine, Department of Epidemiology & Population Health, Stanford, CA 94304, USA; Stanford University School of Medicine, Department of Health Research and Policy, Stanford, CA 94305, USA
  • 74 Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong; The University of Hong Kong, Department of Surgery, Pok Fu Lam, Hong Kong; Hong Kong Sanatorium and Hospital, Cancer Genetics Center and Department of Surgery, Happy Valley, Hong Kong
  • 75 VIB Center for Cancer Biology, Leuven 3001, Belgium; University of Leuven, Laboratory for Translational Genetics, Department of Human Genetics, Leuven 3000, Belgium
  • 76 University of Hawaii Cancer Center, Epidemiology Program, Honolulu, HI 96813, USA
  • 77 Genome Institute of Singapore, Human Genetics Division, Singapore 138672, Singapore
  • 78 Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm 171 76, Sweden; Karolinska University Hospital, Department of Clinical Genetics, Stockholm 171 76, Sweden
  • 79 Pomeranian Medical University, Department of Genetics and Pathology, Szczecin 71-252, Poland
  • 80 University of Eastern Finland, Translational Cancer Research Area, Kuopio 70210, Finland; University of Eastern Finland, Institute of Clinical Medicine, Pathology and Forensic Medicine, Kuopio 70210, Finland; Kuopio University Hospital, Biobank of Eastern Finland, Kuopio 70210, Finland
  • 81 Södersjukhuset, Department of Oncology, Stockholm 118 83, Sweden; Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm 118 83, Sweden
  • 82 University Hospital of Heraklion, Department of Medical Oncology, Heraklion 711 10, Greece
  • 83 University of Munich, Campus Großhadern, Department of Gynecology and Obstetrics, Munich 81377, Germany
  • 84 University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON M5S 1A8, Canada; University Health Network, Laboratory Medicine Program, Toronto, ON M5G 2C4, Canada
  • 85 Helsinki University Hospital, Department of Obstetrics and Gynecology, University of Helsinki, Helsinki 00290, Finland
  • 86 Beckman Research Institute of City of Hope, Department of Population Sciences, Duarte, CA 91010, USA
  • 87 University of North Carolina at Chapel Hill, Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA
  • 88 Mayo Clinic, Department of Health Sciences Research, Rochester, MN 55905, USA
  • 89 King's College London, Research Oncology, Guy's Hospital, London SE1 9RT, UK
  • 90 University of Oulu, Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, Oulu 90220, Finland; Northern Finland Laboratory Centre Oulu, Laboratory of Cancer Genetics and Tumor Biology, Oulu 90220, Finland
  • 91 Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan 20133, Italy
  • 92 Hospital Universitario Puerta de Hierro, Medical Oncology Department, Madrid 28222, Spain
  • 93 UCLH Foundation Trust, Department of Oncology, London NW1 2PG, UK
  • 94 University Hospital of Larissa, Department of Oncology, Larissa 411 10, Greece
  • 95 King's College London, School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, London SE1 1UL, UK
  • 96 Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Familial Breast and Ovarian Cancer, Cologne 50937, Germany; Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Integrated Oncology (CIO), Cologne 50937, Germany; Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne 50931, Germany
  • 97 University of Malaya, Breast Cancer Research Unit, University Malaya Cancer Research Institute, Faculty of Medicine, Kuala Lumpur 50603, Malaysia
  • 98 Academia Sinica, Institute of Biomedical Sciences, Taipei 115, Taiwan; China Medical University, School of Public Health, Taichung 40402, Taiwan
  • 99 Vanderbilt University School of Medicine, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA
  • 100 Netherlands Comprehensive Cancer Organisation (IKNL), Department of Research, Utrecht 3511 DT, the Netherlands; University of Twente, Department of Health Technology and Service Research, Technical Medical Center, Enschede 7522 NB, the Netherlands
  • 101 University Hospital and German Cancer Research Center, National Center for Tumor Diseases, Heidelberg 69120, Germany
  • 102 Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, VIC 3004, Australia; Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, Clayton, VIC 3168, Australia; The University of Melbourne, Department of Clinical Pathology, Melbourne, VIC 3010, Australia
  • 103 BC Cancer, Population Oncology, Vancouver, BC V5Z 1G1, Canada; University of British Columbia, School of Population and Public Health, Vancouver, BC V6T 1Z4, Canada
  • 104 The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, VIC 3010, Australia; Curtin University and University of Western Australia, The Curtin UWA Centre for Genetic Origins of Health and Disease, Perth, WA 6000, Australia
  • 105 University of Eastern Finland, Translational Cancer Research Area, Kuopio 70210, Finland; Kuopio University Hospital, Department of Oncology, Cancer Center, Kuopio 70210, Finland; University of Eastern Finland, Institute of Clinical Medicine, Oncology, Kuopio 70210, Finland
  • 106 Cancer Research Malaysia, Breast Cancer Research Programme, Subang Jaya, Selangor 47500, Malaysia; University of Malaya, Department of Surgery, Faculty of Medicine, Kuala Lumpur 50603, Malaysia
  • 107 Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, NY 10032, USA
  • 108 Leiden University Medical Center, Department of Surgery, Leiden 2333 ZA, the Netherlands
  • 109 University of Birmingham, Institute of Cancer and Genomic Sciences, Birmingham B15 2TT, UK; University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, Oxford OX3 7BN, UK
  • 110 Mayo Clinic, Department of Health Science Research, Division of Epidemiology, Rochester, MN 55905, USA
  • 111 Leuven Cancer Institute, University Hospitals Leuven, Leuven Multidisciplinary Breast Center, Department of Radiology, Leuven 3000, Belgium
  • 112 Karolinska Institutet, Institute of Environmental Medicine, Stockholm 171 77, Sweden; Uppsala University, Department of Surgical Sciences, Uppsala 751 05, Sweden
  • 113 Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm 171 65, Sweden; Södersjukhuset, Department of Oncology, Stockholm 118 83, Sweden
  • 114 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam 1066 CX, the Netherlands; The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Division of Psychosocial Research and Epidemiology, Amsterdam 1066 CX, the Netherlands. Electronic address: [email protected]
Am J Hum Genet, 2020 11 05;107(5):837-848.
PMID: 33022221 DOI: 10.1016/j.ajhg.2020.09.001

Abstract

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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