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Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families.
Yang, Xin; Leslie, Goska; Doroszuk, Alicja; Schneider, Sandra; Allen, Jamie; Decker, Brennan; Dunning, Alison M; Redman, James; Scarth, James; Plaskocinska, Inga; Luccarini, Craig; Shah, Mitul; Pooley, Karen; Dorling, Leila; Lee, Andrew; Adank, Muriel A; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L; Ang, Peter; Barwell, Julian; Bernstein, Jonine L; Bobolis, Kristie; Borg, Åke; Blomqvist, Carl; Claes, Kathleen B M; Concannon, Patrick; Cuggia, Adeline; Culver, Julie O; Damiola, Francesca; de Pauw, Antoine; Diez, Orland; Dolinsky, Jill S; Domchek, Susan M; Engel, Christoph; Evans, D Gareth; Fostira, Florentia; Garber, Judy; Golmard, Lisa; Goode, Ellen L; Gruber, Stephen B; Hahnen, Eric; Hake, Christopher; Heikkinen, Tuomas; Hurley, Judith E; Janavicius, Ramunas; Kleibl, Zdenek; Kleiblova, Petra; Konstantopoulou, Irene; Kvist, Anders.
Afiliação
  • Yang X; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Leslie G; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Doroszuk A; Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, United Kingdom.
  • Schneider S; Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, United Kingdom.
  • Allen J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Decker B; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Dunning AM; Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
  • Redman J; Department of Pathology, Brigham and Women's Hospital, Boston, MA.
  • Scarth J; Centre for Cancer Genetic Epidemiology, Department of Oncology,University of Cambridge, Cambridge, United Kingdom.
  • Plaskocinska I; Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, United Kingdom.
  • Luccarini C; Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, United Kingdom.
  • Shah M; Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, United Kingdom.
  • Pooley K; Centre for Cancer Genetic Epidemiology, Department of Oncology,University of Cambridge, Cambridge, United Kingdom.
  • Dorling L; Centre for Cancer Genetic Epidemiology, Department of Oncology,University of Cambridge, Cambridge, United Kingdom.
  • Lee A; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Adank MA; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Adlard J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Aittomäki K; Family Cancer Clinic, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
  • Andrulis IL; Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, United Kingdom.
  • Ang P; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Barwell J; Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Bernstein JL; Laboratory of Molecular Oncology, Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore.
  • Bobolis K; Leicestershire Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
  • Borg Å; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Blomqvist C; Clinical Cancer Genomics Community Research Network, City of Hope, Duarte, CA.
  • Claes KBM; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
  • Concannon P; Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Cuggia A; Centre for Medical Genetics, Ghent University, Ghent, Belgium.
  • Culver JO; University of Florida Genetics Institute, University of Florida, Gainesville, FL.
  • Damiola F; The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
  • de Pauw A; The Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
  • Diez O; Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
  • Dolinsky JS; Biopathologie, Centre Léon Bérard, Lyon, France.
  • Domchek SM; Service de Génétique, Institut Curie, Paris, France.
  • Engel C; Oncogenetics Group, Clinical and Molecular Genetics Area, Vall d'Hebron Institute of Oncology (VHIO), University Hospital, Vall d'Hebron, Barcelona, Spain.
  • Evans DG; Ambry Genetics, Aliso Viejo, CA.
  • Fostira F; Department ofMedicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
  • Garber J; Prospective Registry of Multiplex Testing (PROMPT), United States and Europe.
  • Golmard L; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
  • Goode EL; Division of Evolution and Genomic Sciences, University of Manchester; Manchester Centre for Genomic Medicine, St Mary's Hospital-Manchester University Hospitals NHS Foundation Trust; and Manchester Academic Health Science Centre, Manchester, United Kingdom.
  • Gruber SB; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research "Demokritos," Athens, Greece.
  • Hahnen E; Prospective Registry of Multiplex Testing (PROMPT), United States and Europe.
  • Hake C; Dana-Farber Cancer Institute, Boston, MA.
  • Heikkinen T; Service de Génétique, Institut Curie, Paris, France.
  • Hurley JE; Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
  • Janavicius R; City of Hope National Medical Center, Duarte, CA.
  • Kleibl Z; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Kleiblova P; Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.
  • Konstantopoulou I; Clinical Cancer Genomics Community Research Network, City of Hope, Duarte, CA.
  • Kvist A; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
J Clin Oncol ; 38(7): 674-685, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841383
ABSTRACT

PURPOSE:

To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized.

METHODS:

We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.

RESULTS:

We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.

CONCLUSION:

These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: J Clin Oncol 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 Idioma: Inglês Revista: J Clin Oncol Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Reino Unido
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