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Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.
Barnes, Daniel R; Rookus, Matti A; McGuffog, Lesley; Leslie, Goska; Mooij, Thea M; Dennis, Joe; Mavaddat, Nasim; Adlard, Julian; Ahmed, Munaza; Aittomäki, Kristiina; Andrieu, Nadine; Andrulis, Irene L; Arnold, Norbert; Arun, Banu K; Azzollini, Jacopo; Balmaña, Judith; Barkardottir, Rosa B; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Bialkowska, Katarzyna; Blanco, Amie M; Blok, Marinus J; Bonanni, Bernardo; Boonen, Susanne E; Borg, Åke; Bozsik, Aniko; Bradbury, Angela R; Brennan, Paul; Brewer, Carole; Brunet, Joan; Buys, Saundra S; Caldés, Trinidad; Caligo, Maria A; Campbell, Ian; Christensen, Lise Lotte; Chung, Wendy K; Claes, Kathleen B M; Colas, Chrystelle; Collonge-Rame, Marie-Agnès; Cook, Jackie; Daly, Mary B; Davidson, Rosemarie; de la Hoya, Miguel; de Putter, Robin; Delnatte, Capucine; Devilee, Peter; Diez, Orland; Ding, Yuan Chun; Domchek, Susan M.
Afiliação
  • Barnes DR; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. drb54@medschl.cam.ac.uk.
  • Rookus MA; The Netherlands Cancer Institute, Department of Epidemiology (PSOE), Amsterdam, The Netherlands.
  • McGuffog L; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Leslie G; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Mooij TM; The Netherlands Cancer Institute, Department of Epidemiology (PSOE), Amsterdam, The Netherlands.
  • Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Mavaddat N; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Adlard J; Chapel Allerton Hospital, Yorkshire Regional Genetics Service, Leeds, UK.
  • Ahmed M; Great Ormond Street Hospital for Children NHS Trust, North East Thames Regional Genetics Service, London, UK.
  • Aittomäki K; University of Helsinki, Department of Clinical Genetics, Helsinki University Hospital, Helsinki, Finland.
  • Andrieu N; Inserm U900, Genetic Epidemiology of Cancer team, Paris, France.
  • Andrulis IL; Institut Curie, Paris, France.
  • Arnold N; Mines ParisTech, Fontainebleau, France.
  • Arun BK; Department of Life & Health Sciences, PSL University, Paris, France.
  • Azzollini J; Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON, Canada.
  • Balmaña J; University of Toronto, Department of Molecular Genetics, Toronto, ON, Canada.
  • Barkardottir RB; University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Department of Gynaecology and Obstetrics, Kiel, Germany.
  • Barrowdale D; University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Institute of Clinical Molecular Biology, Kiel, Germany.
  • Benitez J; University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, TX, USA.
  • Berthet P; Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Unit of Medical Genetics, Department of Medical Oncology and Hematology, Milan, Italy.
  • Bialkowska K; Vall d'Hebron Institute of Oncology, High Risk and Cancer Prevention Group, Barcelona, Spain.
  • Blanco AM; University Hospital of Vall d'Hebron, Department of Medical Oncology, Barcelona, Spain.
  • Blok MJ; Landspitali University Hospital, Department of Pathology, Reykjavik, Iceland.
  • Bonanni B; University of Iceland, BMC (Biomedical Centre), Faculty of Medicine, Reykjavik, Iceland.
  • Boonen SE; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Borg Å; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
  • Bozsik A; Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, Spain.
  • Bradbury AR; Centre François Baclesse, Département de Biopathologie, Caen, France.
  • Brennan P; Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland.
  • Brewer C; University of California San Francisco, Cancer Genetics and Prevention Program, San Francisco, CA, USA.
  • Brunet J; Maastricht University Medical Center, Department of Clinical Genetics, Maastricht, The Netherlands.
  • Buys SS; IEO, European Institute of Oncology IRCCS, Division of Cancer Prevention and Genetics, Milan, Italy.
  • Caldés T; Zealand University Hospital, Clinical Genetic Unit, Department of Paediatrics, Roskilde, Denmark.
  • Caligo MA; Lund University, Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund, Sweden.
  • Campbell I; National Institute of Oncology, Department of Molecular Genetics, Budapest, Hungary.
  • Christensen LL; Perelman School of Medicine at the University of Pennsylvania, Department of Medicine, Abramson Cancer Center, Philadelphia, PA, USA.
  • Chung WK; Institute of Genetic Medicine, International Centre for Life, Northern Genetic Service, Newcastle upon Tyne, UK.
  • Claes KBM; Royal Devon & Exeter Hospital, Department of Clinical Genetics, Exeter, UK.
  • Colas C; ONCOBELL-IDIBELL-IDIBGI-IGTP, Catalan Institute of Oncology, CIBERONC, Hereditary Cancer Program, Barcelona, Spain.
  • Collonge-Rame MA; University Hospital, SOD Genetica Molecolare, Pisa, Italy.
  • Cook J; Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
  • Daly MB; The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC, Australia.
  • Davidson R; Aarhus University Hospital, Department of Clinical Medicine,, Aarhus, Denmark.
  • de la Hoya M; Columbia University, Departments of Pediatrics and Medicine, New York, NY, USA.
  • de Putter R; Ghent University, Centre for Medical Genetics, Ghent, Belgium.
  • Delnatte C; Institut Curie, Service de Génétique, Paris, France.
  • Ding YC; CHU de Besançon, Service de Génétique, Besançon, France.
  • Domchek SM; Sheffield Children's Hospital, Sheffield Clinical Genetics Service, Sheffield, UK.
Genet Med ; 22(10): 1653-1666, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32665703
ABSTRACT

PURPOSE:

We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.

METHODS:

Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.

RESULTS:

The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10-12) carriers. The associations in the prospective cohort were similar.

CONCLUSION:

Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo de etiologia / Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Genet Med Assunto da revista: Genética Médica Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Reino Unido

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo de etiologia / Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Genet Med Assunto da revista: Genética Médica Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Reino Unido
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