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https://repository.monashhealth.org/monashhealthjspui/handle/1/29339| Title: | Cancer risks associated with germline PALB2 pathogenic variants: An international study of 524 families. | Authors: | Hake C.;Redman J.;Kleibl Z.;Kleiblova P.;Konstantopoulou I.;Kvist A.;Laduca H.;Lee A.S.G.;Lesueur F.;Maher E.R.;Mannermaa A.;Manoukian S.;McFarland R.;McKinnon W.;Meindl A.;Metcalfe K.;Taib N.A.M.;Moilanen J.;Nathanson K.L.;Neuhausen S.;Ng P.S.;Nguyen-Dumont T.;Nielsen S.M.;Obermair F.;Offit K.;Olopade O.I.;Ottini L.;Penkert J.;Pylkas K.;Radice P.;Ramus S.J.;Rudaitis V.;Side L.;Silva-Smith R.;Silvestri V.;Skytte A.-B.;Slavin T.;Soukupova J.;Tondini C.;Trainer A.H.;Unzeitig G.;Usha L.;Van Overeem Hansen T.;Whitworth J.;Wood M.;Yip C.H.;Yoon S.-Y.;Yussuf A.;Zogopoulos G.;Goldgar D.;Hopper J.L.;Chenevix-Trench G.;Pharoah P.;George S.H.L.;Balmana J.;Houdayer C.;James P.;El-Haffaf Z.;Ehrencrona H.;Janatova M.;Peterlongo P.;Nevanlinna H.;Schmutzler R.;Teo S.-H.;Robson M.;Pal T.;Couch F.;Weitzel J.N.;Elliott A.;Southey M.;Winqvist R.;Easton D.F.;Foulkes W.D.;Antoniou A.C.;Tischkowitz M.;Yang X.;Leslie G.;Doroszuk A.;Schneider S.;Allen J. ;Decker B.;Dunning A.M.;Scarth J.;Plaskocinska I.;Luccarini C.;Shah M.;Pooley K.;Dorling L.;Leei A.;Adank M.A.;Adlard J.;Aittomaki K.;Andrulis I.L.;Ang P.;Barwell J.;Bernstein J.L.;Bobolis K.;Borg A.;Blomqvist C.;Claes K.B.M.;Concannon P.;Cuggia A.;Culver J.O.;Damiola F.;De Pauw A.;Diez O.;Dolinsky J.S.;Domchek S.M.;Engel C.;Evans D.G.;Fostira F.;Garber J.;Golmard L.;Goode E.L.;Gruber S.B.;Hahnen E.;Heikkinen T.;Hurley J.E.;Janavicius R. | Monash Health Department(s): | Monash University - School of Clinical Sciences at Monash Health | Institution: | (Yang, Leslie, Allen, Decker, Pooley, Dorling, Leei, Pharoah, Easton, Antoniou) Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (Doroszuk, Schneider, Redman, Scarth, Plaskocinska, Maher, Whitworth, Tischkowitz) Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, United Kingdom (Decker) Cancer Genetics Branch, National Human Genome Research Institute National Institutes of Health, Bethesda, MD, United States (Decker) Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States (Dunning, Luccarini, Shah) Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom (Adank) Family Cancer Clinic, Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital, Amsterdam, Netherlands (Adlard) Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, United Kingdom (Aittomaki) Department of Clinical Genetics, Helsinki University Hospital University of Helsinki, Helsinki, Finland (Andrulis) Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada (Ang) Laboratory of Molecular Oncology, Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore, Singapore (Barwell, Lee) Leicestershire Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (Bernstein) Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States (Bobolis, Hake, Slavin, Unzeitig, Usha, Weitzel) Clinical Cancer Genomics Community Research Network, City of Hope Duarte, CA, United States (Borg, Kvist) Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden (Blomqvist) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland (Claes) Centre for Medical Genetics, Ghent University, Ghent, Belgium (Concannon) University of Florida Genetics Institute, University of Florida, Gainesville, FL, United States (Cuggia, Zogopoulos, Foulkes) Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada (Cuggia, Zogopoulos) Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada (Culver) Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, United States (Damiola) Biopathologie, Centre Leon Berard, Lyon, France (De Pauw, Golmard, Houdayer) Service de Genetique, Institut Curie, Paris, France (Diez, Balmana) Oncogenetics Group, Clinical and Molecular Genetics Area, Vall d'Hebron Institute of Oncology (VHIO), University Hospital, Vall d'Hebron, Barcelona, Spain (Dolinsky, Laduca, McFarland, Yussuf, Elliott) Ambry Genetics, Aliso Viejo, CA, United States (Domchek, Nathanson) Department OfMedicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States (Domchek, Garber, Offit, Balmana, Robson, Couch) Prospective Registry of Multiplex Testing (PROMPT), United States and Europe, United States (Engel) Institute for Medical Informatics, Statistics and Epidemiology University of Leipzig, Leipzig, Germany (Evans) Division of Evolution and Genomic Sciences, University of Manchester, Manchester Centre for Genomic Medicine, St Mary's Hospital-Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom (Fostira, Konstantopoulou) Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece (Garber) Dana-Farber Cancer Institute, Boston, MA, United States (Goode) Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States (Gruber) City of Hope National Medical Center, Duarte, CA, United States (Hahnen, Schmutzler) Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany (Hahnen, Schmutzler) Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany (Heikkinen, Nevanlinna) Department of Obstetrics and Gynecology, Helsinki University Hospital University of Helsinki, Helsinki, Finland (Hurley) Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL, United States (Janavicius, Rudaitis) Hematology, Oncology and Transfusion Medicine Center, Department of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania (Janavicius) State Research Institute Innovative Medicine Center, Vilnius, Lithuania (Kleibl, Kleiblova, Soukupova, Janatova) Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia (Kleiblova) Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czechia (Lee) Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore (Lee) SingHealth Duke-NUS Oncology Academic Clinical Programme (ONCO ACP), Duke-NUS Medical School, Singapore, Singapore (Lesueur) INSERM U900, Institut Curie, PSL University, Mines ParisTech, Paris, France (Mannermaa) Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland (Manoukian) Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy (McFarland) Department of Epidemiology, University of California, Irvine, Irvine, CA, United States (McKinnon, Wood) Familial Cancer Program, University of Vermont Cancer Center, Burlington, VT, United States (Meindl) Department of Gynecology and Obstetrics, Ludwig-Maximilians University of Munich, Munich, Germany (Metcalfe) Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada (Taib, Ng, Teo) University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia (Moilanen) Department of Clinical Genetics, Oulu University Hospital, Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu, Oulu, Finland (Neuhausen) Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, United States (Ng, Yip, Yoon, Teo) Cancer Research Malaysia, Subang Jaya Selangor, Malaysia (Nguyen-Dumont, Southey) Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia (Nguyen-Dumont, Southey) Precision Medicine, School of Clinical Sciences, Monash Health Monash University, Clayton, VIC, Australia (Nielsen, Olopade) Center for Clinical Cancer Genetics, University of Chicago, Chicago, IL, United States (Obermair) Institute of Medical Genetics, Kepler University Hospital Linz, Laboratory for Molecular Biology and Tumor Cytogenetics Ordensklinikum Linz, Linz, Austria (Offit) Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States (Ottini, Silvestri) Department of Molecular Medicine, University la Sapienza, Rome, Italy (Penkert) Department of Human Genetics, Hannover Medical School, Hannover, Germany (Pylkas, Winqvist) Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Northern Finland Laboratory Centre, Oulu, Finland (Radice) Unit of Molecular Basis of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy (Ramus) School of Women's and Children's Health, Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW, Australia (Ramus) Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia (Side) Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, United Kingdom (Silva-Smith) Department of Genetics, University of Miami, Miller School of Medicine, Miami, FL, United States (Skytte) Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark (Slavin, Weitzel) Department of Medical Oncology, Division of Clinical Cancer Genomics, City of Hope, Duarte, CA, United States (Tondini) Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy (Trainer, James) Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia (Trainer, James) Parkville Familial Cancer Centre, Peter MacCallum Cancer Center, Melbourne, VIC, Australia (Van Overeem Hansen) Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (Van Overeem Hansen) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (Goldgar) Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, United States (Hopper) Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia (Chenevix-Trench) Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia (George) Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL, United States (Houdayer) Genetics Department, F76000 and Normandy University, UNIROUEN INSERM U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France (El-Haffaf) Department of Genetics, Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada (Ehrencrona) Department of Clinical Genetics and Pathology, Department of Laboratory Medicine, Office for Medical Services, Lund, Sweden (Ehrencrona) Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden (Peterlongo) Genome Diagnostics Program, IFOM-The FIRC Institute for Molecular Oncology, Milan, Italy (Robson) Breast Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States (Pal) Vanderbilt-Ingram Cancer Center, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States (Couch) Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States (Foulkes) Departments of Human Genetics, Oncology, and Medicine, McGill University, Montreal, QC, Canada | Issue Date: | 9-Mar-2020 | Copyright year: | 2020 | Publisher: | American Society of Clinical Oncology (E-mail: jcoservice@asco.org) | Place of publication: | United States | Publication information: | Journal of Clinical Oncology. 38 (7) (pp 674-685), 2020. Date of Publication: 01 Mar 2020. | Journal: | Journal of Clinical Oncology | 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 x 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 x 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 x 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 x 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.Copyright © 2019 by American Society of Clinical Oncology. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1200/JCO.19.01907 | PubMed URL: | 31841383 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31841383] | ISSN: | 0732-183X | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29339 | Type: | Article | Subjects: | *partner and localizer of BRCA2/ec [Endogenous Compound] germline mutation female family history *colorectal cancer cohort analysis *cancer risk cancer family *breast cancer article adult aged human knowledge major clinical study male *male breast cancer *ovary cancer *pancreas cancer priority journal *prostate cancer retrospective study risk factor segregation analysis partner and localizer of BRCA2 germline mutation family history colorectal cancer cancer risk cancer family breast cancer aged knowledge breast cancer ovary cancer pancreas cancer prostate cancer segregation analysis retrospective study *prostate cancer priority journal *pancreas cancer *ovary cancer *male breast cancer male major clinical study segregation analysis risk factor *breast cancer Article aged adult knowledge human germline mutation female family history *colorectal cancer cohort analysis *cancer risk cancer family |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
| Appears in Collections: | Articles |
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