Breast cancer risks associated with missense variants in breast cancer susceptibility genes.

Breast Neoplasms / genetics Case-Control Studies Female Genetic Predisposition to Disease Humans Mutation, Missense
Breast cancer Genetic epidemiology Missense variants Risk prediction

Journal

Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844

Informations de publication

Date de publication:
18 05 2022
Historique:
received: 20 08 2021
accepted: 04 05 2022
entrez: 18 5 2022
pubmed: 19 5 2022
medline: 21 5 2022
Statut: epublish

Résumé

Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47-2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.

Sections du résumé

BACKGROUND
Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain.
METHODS
We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated.
RESULTS
The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47-2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set.
CONCLUSIONS
These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.

Identifiants

DOI: 10.1186/s13073-022-01052-8 PMID: 35585550 PMC: PMC9116026
pubmed: 35585550
doi: 10.1186/s13073-022-01052-8
pii: 10.1186/s13073-022-01052-8
pmc: PMC9116026
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

51

Subventions

Organisme : Wellcome Trust
ID : 203477/Z/16/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C1287/A16563
Pays : United Kingdom
Organisme : Wellcome Trust
ID : v203477/Z/16/Z
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Leila Dorling (L)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.

Sara Carvalho (S)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.

Jamie Allen (J)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.

Michael T Parsons (MT)

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Cristina Fortuno (C)

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Anna González-Neira (A)

Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029, Madrid, Spain.

Stephan M Heijl (SM)

Bio-Prodict, Nijmegen, The Netherlands.

Muriel A Adank (MA)

Family Cancer Clinic, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, The Netherlands.

Thomas U Ahearn (TU)

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.

Irene L Andrulis (IL)

Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.

Päivi Auvinen (P)

Translational Cancer Research Area, University of Eastern Finland, 70210, Kuopio, Finland.
Institute of Clinical Medicine, Oncology, University of Eastern Finland, 70210, Kuopio, Finland.
Department of Oncology, Cancer Center, Kuopio University Hospital, 70210, Kuopio, Finland.

Heiko Becher (H)

Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.

Matthias W Beckmann (MW)

Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), 91054, Erlangen, Germany.

Sabine Behrens (S)

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Marina Bermisheva (M)

Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, 450054, Russia.

Natalia V Bogdanova (NV)

Department of Radiation Oncology, Hannover Medical School, 30625, Hannover, Germany.
Gynaecology Research Unit, Hannover Medical School, 30625, Hannover, Germany.
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, 223040, Minsk, Belarus.

Stig E Bojesen (SE)

Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.

Manjeet K Bolla (MK)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.

Michael Bremer (M)

Department of Radiation Oncology, Hannover Medical School, 30625, Hannover, Germany.

Ignacio Briceno (I)

Medical Faculty, Universidad de La Sabana, 140013, Bogota, Colombia.

Nicola J Camp (NJ)

Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.

Archie Campbell (A)

Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, EH16 4UX, UK.

Jose E Castelao (JE)

Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, 36312, Vigo, Spain.

Jenny Chang-Claude (J)

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.

Stephen J Chanock (SJ)

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.

Georgia Chenevix-Trench (G)

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

J Margriet Collée (JM)

Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands.

Kamila Czene (K)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.

Joe Dennis (J)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.

Thilo Dörk (T)

Gynaecology Research Unit, Hannover Medical School, 30625, Hannover, Germany.

Mikael Eriksson (M)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.

D Gareth Evans (DG)

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, M13 9WL, 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, M13 9WL, UK.
Nightingale & Genesis Prevention Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, M23 9LT, UK.
NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.

Peter A Fasching (PA)

Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), 91054, Erlangen, Germany.
David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.

Jonine Figueroa (J)

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.
Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, EH16 4UX, UK.
Cancer Research UK Edinburgh Centre, The University of Edinburgh, Edinburgh, EH4 2XR, UK.

Henrik Flyger (H)

Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.

Marike Gabrielson (M)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.

Manuela Gago-Dominguez (M)

Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, , 15706, Santiago de Compostela, Spain.
Moores Cancer Center, University of California San Diego, La Jolla, CA, 92037, USA.

Montserrat García-Closas (M)

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.

Graham G Giles (GG)

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.

Gord Glendon (G)

Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.

Pascal Guénel (P)

Team "Exposome and Heredity", CESP, Inserm, Gustave Roussy, University Paris-Saclay, UVSQ, Villejuif, France.

Melanie Gündert (M)

Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, 69120, Heidelberg, Germany.
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.

Andreas Hadjisavvas (A)

Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, 2371, Nicosia, Cyprus.
Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, 2371, Nicosia, Cyprus.

Eric Hahnen (E)

Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937, Cologne, Germany.
Center for Integrated Oncology (CIO), Faculty of Medicine, University Hospital Cologne, University of Cologne, 50937, Cologne, Germany.

Per Hall (P)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
Department of Oncology, 118 83, Södersjukhuset, Stockholm, Sweden.

Ute Hamann (U)

Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Elaine F Harkness (EF)

Nightingale & Genesis Prevention Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, M23 9LT, UK.
NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.
Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PT, UK.

Mikael Hartman (M)

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
Department of Surgery, National University Health System, Singapore, 119228, Singapore.
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, 119228, Singapore.

Frans B L Hogervorst (FBL)

Family Cancer Clinic, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, The Netherlands.

Antoinette Hollestelle (A)

Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, 3015 GD, The Netherlands.

Reiner Hoppe (R)

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376, Stuttgart, Germany.
University of Tübingen, 72074, Tübingen, Germany.

Anthony Howell (A)

NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.
Division of Cancer Sciences, University of Manchester, Manchester, M13 9PL, UK.

Anna Jakubowska (A)

Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.
Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, 71-252, Szczecin, Poland.

Audrey Jung (A)

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Elza Khusnutdinova (E)

Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, 450054, Russia.
Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, 450000, Russia.

Sung-Won Kim (SW)

Department of Surgery, Daerim Saint Mary's Hospital, Seoul, 07442, Korea.

Yon-Dschun Ko (YD)

Department of Internal Medicine, Johanniter GmbH Bonn, Johanniter Krankenhaus, 53113, Bonn, Germany.

Vessela N Kristensen (VN)

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0450, Oslo, Norway.
Department of Medical Genetics, Oslo University Hospital and University of Oslo, 0379, Oslo, Norway.

Inge M M Lakeman (IMM)

Department of Human Genetics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
Department of Clinical Genetics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.

Jingmei Li (J)

Department of Surgery, National University Health System, Singapore, 119228, Singapore.
Human Genetics Division, Genome Institute of Singapore, Singapore, 138672, Singapore.

Annika Lindblom (A)

Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden.
Department of Clinical Genetics, Karolinska University Hospital, 171 76, Stockholm, Sweden.

Maria A Loizidou (MA)

Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, 2371, Nicosia, Cyprus.
Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, 2371, Nicosia, Cyprus.

Artitaya Lophatananon (A)

Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PL, UK.

Jan Lubiński (J)

Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.

Craig Luccarini (C)

Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.

Michael J Madsen (MJ)

Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.

Arto Mannermaa (A)

Translational Cancer Research Area, University of Eastern Finland, 70210, Kuopio, Finland.
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Biobank of Eastern Finland, Kuopio University Hospital, Kuopio, Finland.

Mehdi Manoochehri (M)

Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Sara Margolin (S)

Department of Oncology, 118 83, Södersjukhuset, Stockholm, Sweden.
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 118 83, Stockholm, Sweden.

Dimitrios Mavroudis (D)

Department of Medical Oncology, University Hospital of Heraklion, 711 10, Heraklion, Greece.

Roger L Milne (RL)

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.

Nur Aishah Mohd Taib (NA)

Breast Cancer Research Unit, Faculty of Medicine, University Malaya Cancer Research Institute, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Department of Surgery, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Kenneth Muir (K)

Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PL, UK.

Heli Nevanlinna (H)

Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290, Helsinki, Finland.

William G Newman (WG)

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, M13 9WL, 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, M13 9WL, UK.
NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.

Jan C Oosterwijk (JC)

Department of Genetics, University Medical Center Groningen, University Groningen, Groningen, 9713 GZ, The Netherlands.

Sue K Park (SK)

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, 03080, Korea.
Convergence Graduate Program in Innovative Medical Science, Seoul National University College of Medicine, Seoul, 03080, South Korea.
Cancer Research Institute, Seoul National University, Seoul, 03080, Korea.

Paolo Peterlongo (P)

Genome Diagnostics Program, IFOM - the FIRC Institute of Molecular Oncology, 20139, Milan, Italy.

Paolo Radice (P)

Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale Dei Tumori (INT), 20133, Milan, Italy.

Emmanouil Saloustros (E)

Department of Oncology, University Hospital of Larissa, 411 10, Larissa, Greece.

Elinor J Sawyer (EJ)

School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London, UK.

Rita K Schmutzler (RK)

Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937, Cologne, Germany.
Center for Integrated Oncology (CIO), Faculty of Medicine, University Hospital Cologne, University of Cologne, 50937, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.

Mitul Shah (M)

Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.

Xueling Sim (X)

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.

Melissa C Southey (MC)

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.
Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.

Harald Surowy (H)

Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, 69120, Heidelberg, Germany.

Maija Suvanto (M)

Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290, Helsinki, Finland.

Ian Tomlinson (I)

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, OX3 7BN, UK.

Diana Torres (D)

Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Institute of Human Genetics, Pontificia Universidad Javeriana, 110231, Bogota, Colombia.

Thérèse Truong (T)

Team "Exposome and Heredity", CESP, Inserm, Gustave Roussy, University Paris-Saclay, UVSQ, Villejuif, France.

Christi J van Asperen (CJ)

Department of Clinical Genetics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.

Regina Waltes (R)

Gynaecology Research Unit, Hannover Medical School, 30625, Hannover, Germany.

Qin Wang (Q)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.

Xiaohong R Yang (XR)

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.

Paul D P Pharoah (PDP)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.

Marjanka K Schmidt (MK)

Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, The Netherlands.
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, The Netherlands.

Javier Benitez (J)

Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029, Madrid, Spain.
Biomedical Network On Rare Diseases (CIBERER), 28029, Madrid, Spain.

Bas Vroling (B)

Bio-Prodict, Nijmegen, The Netherlands.
Centre for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center, Nijmegen, The Netherlands.

Alison M Dunning (AM)

Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.

Soo Hwang Teo (SH)

Breast Cancer Research Unit, Faculty of Medicine, University Malaya Cancer Research Institute, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya, 47500, Selangor, Malaysia.

Anders Kvist (A)

Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, 22381, Lund, Sweden.

Miguel de la Hoya (M)

Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), 28040, Madrid, Spain.

Peter Devilee (P)

Department of Human Genetics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.

Amanda B Spurdle (AB)

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Maaike P G Vreeswijk (MPG)

Department of Human Genetics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.

Douglas F Easton (DF)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK. dfe20@medschl.cam.ac.uk.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK. dfe20@medschl.cam.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Breast cancer risks associated with missense...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Breast cancer risks associated with missense...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Breast cancer risks associated with missense...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Breast cancer risks associated with missense...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation faux-sens › Breast cancer risks associated with missense...