Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families

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Yang, XinUniversity of Cambridge (author)

Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families

Article/chapterEnglish2020

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2020

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LIBRIS-ID:oai:lup.lub.lu.se:9c2cb720-8f1e-451d-a459-53260d1bafbb
https://lup.lub.lu.se/record/9c2cb720-8f1e-451d-a459-53260d1bafbbURI
https://doi.org/10.1200/JCO.19.01907DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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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 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 × 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.

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Leslie, GoskaUniversity of Cambridge (author)
Doroszuk, AlicjaUniversity of Cambridge (author)
Schneider, SandraUniversity of Cambridge (author)
Allen, JamieUniversity of Cambridge (author)
Decker, BrennanBrigham and Women's Hospital / Harvard Medical School,University of Cambridge,National Human Genome Research Institute (author)
Dunning, Alison M.University of Cambridge (author)
Redman, JamesUniversity of Cambridge (author)
Scarth, JamesUniversity of Cambridge (author)
Plaskocinska, IngaUniversity of Cambridge (author)
Luccarini, CraigUniversity of Cambridge (author)
Shah, MitulUniversity of Cambridge (author)
Pooley, KarenUniversity of Cambridge (author)
Dorling, LeilaUniversity of Cambridge (author)
Leei, AndrewUniversity of Cambridge (author)
Adank, Muriel A.Antoni Van Leeuwenhoek Hospital (author)
Adlard, JulianChapel Allerton Hospital (author)
Aittomäki, KristiinaHelsinki University Central Hospital (author)
Andrulis, Irene L.Mount Sinai Hospital of University of Toronto (author)
Ang, PeterNational Cancer Centre Singapore (author)
Barwell, JulianUniversity Hospitals of Leicester NHS Trust (author)
Bernstein, Jonine L.Memorial Sloan-Kettering Cancer Center (author)
Bobolis, KristieClinical Cancer Genomics Community Research Network (author)
Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-abo (author)
Blomqvist, CarlHelsinki University Central Hospital (author)
Claes, Kathleen B.M.Ghent University Hospital (author)
Concannon, PatrickUniversity of Florida (author)
Cuggia, AdelineMcGill University (author)
Culver, Julie O.University of Southern California (author)
Damiola, FrancescaCentre Léon Bérard (author)
De Pauw, AntoineCurie Institute, Paris (author)
Diez, OrlandVall d’Hebron Institute of Oncology (author)
Dolinsky, Jill S.Ambry Genetics Corporation (author)
Domchek, Susan M.University of Pennsylvania,Prospective registry of multiplex testing (PROMPT) (author)
Engel, ChristophLeipzig University (author)
Evans, D. GarethUniversity of Manchester (author)
Fostira, FlorentiaNational Centre for Scientific Research Demokritos (author)
Garber, JudyProspective registry of multiplex testing (PROMPT),Dana-Farber Cancer Institute (author)
Golmard, LisaCurie Institute, Paris (author)
Goode, Ellen L.Mayo Clinic Minnesota (author)
Gruber, Stephen B.Beckman Research Institute of City of Hope (author)
Hahnen, EricUniversity of Cologne,University Hospital of Cologne (author)
Hake, ChristopherClinical Cancer Genomics Community Research Network (author)
Heikkinen, TuomasHelsinki University Central Hospital (author)
Hurley, Judith E.University of Miami (author)
Janavicius, RamunasState Research Institute Innovative Medicine Center,Vilnius University Hospital (author)
Kleibl, ZdenekGeneral University Hospital in Prague (author)
Kleiblova, PetraCharles University in Prague,General University Hospital in Prague (author)
Konstantopoulou, IreneNational Centre for Scientific Research Demokritos (author)
Kvist, AndersLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)ekol-akv (author)
Laduca, HollyAmbry Genetics Corporation (author)
Lee, Ann S.G.Duke–NUS Medical School,University Hospitals of Leicester NHS Trust,National University of Singapore (author)
Lesueur, FabiennePSL University (author)
Maher, Eamonn R.University of Cambridge (author)
Mannermaa, ArtoUniversity of Eastern Finland (author)
Manoukian, SiranoushIstituto Nazionale dei Tumori (author)
McFarland, RachelAmbry Genetics Corporation,University of California, Irvine (author)
McKinnon, WendyUniversity of Vermont (author)
Meindl, AlfonsLudwig-Maximilian University of Munich (author)
Metcalfe, KellyUniversity of Toronto (author)
Taib, Nur Aishah MohdUniversity of Malaya (author)
Moilanen, JukkaOulu University Hospital (author)
Nathanson, Katherine L.University of Pennsylvania (author)
Neuhausen, SusanBeckman Research Institute of City of Hope (author)
Ng, Pei SzeUniversity of Malaya,Cancer Research Initiatives Foundation (author)
Nguyen-Dumont, TuUniversity of Melbourne,Monash University (author)
Nielsen, Sarah M.University of Chicago (author)
Obermair, FlorianKepler University Hospital Linz (author)
Offit, KennethMemorial Sloan-Kettering Cancer Center (author)
Olopade, Olufunmilayo I.University of Chicago (author)
Ottini, LauraSapienza University of Rome (author)
Penkert, JudithHannover Medical School (author)
Pylkäs, KatriUniversity of Oulu (author)
Goldgar, DavidIstituto Nazionale dei Tumori (author)
Ramus, Susan J.Garvan Institute of Medical Research,University of New South Wales (author)
Rudaitis, ViliusVilnius University Hospital (author)
Side, LucyPrincess Anne Hospital (author)
Silva-Smith, RachelUniversity of Miami (author)
Silvestri, ValentinaSapienza University of Rome (author)
Skytte, Anne BineAarhus University Hospital (author)
Slavin, ThomasBeckman Research Institute of City of Hope,Clinical Cancer Genomics Community Research Network (author)
Soukupova, JanaGeneral University Hospital in Prague (author)
Tondini, CarloPapa Giovanni XXIII Hospital (author)
Trainer, Alison H.University of Melbourne,Peter MacCallum Cancer Centre (author)
Unzeitig, GaryClinical Cancer Genomics Community Research Network (author)
Usha, LydiaClinical Cancer Genomics Community Research Network (author)
Van Overeem Hansen, ThomasCopenhagen University Hospital (author)
Whitworth, JamesUniversity of Cambridge (author)
Wood, MarieUniversity of Vermont (author)
Yip, Cheng HarCancer Research Initiatives Foundation (author)
Yoon, Sook YeeCancer Research Initiatives Foundation (author)
Yussuf, AmalAmbry Genetics Corporation (author)
Zogopoulos, GeorgeMcGill University (author)
Radice, PaoloHuntsman Cancer Institute (author)
Hopper, John L.University of Melbourne (author)
Chenevix-Trench, GeorgiaQIMR Berghofer Medical Research Institute (author)
Pharoah, PaulUniversity of Cambridge (author)
George, Sophia H.L.University of Miami (author)
Balmaña, JudithProspective registry of multiplex testing (PROMPT),Vall d’Hebron Institute of Oncology (author)
Houdayer, ClaudeCurie Institute, Paris,Rouen University Hospital (author)
James, PaulUniversity of Melbourne,Peter MacCallum Cancer Centre (author)
El-Haffaf, ZakiUniversity Of Montreal Health Center (CRCHUM) (author)
Ehrencrona, HansLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-hen (author)
Janatova, MarketaGeneral University Hospital in Prague (author)
Peterlongo, PaoloIFOM - The FIRC Institute of Molecular Oncology (author)
Nevanlinna, HeliHelsinki University Central Hospital (author)
Schmutzler, RitaUniversity Hospital of Cologne,University of Cologne (author)
Teo, Soo HwangCancer Research Initiatives Foundation,University of Malaya (author)
Robson, MarkMemorial Sloan-Kettering Cancer Center,Prospective registry of multiplex testing (PROMPT) (author)
Pal, TuyaVanderbilt University (author)
Couch, FergusMayo Clinic Minnesota (author)
Weitzel, Jeffrey N.Beckman Research Institute of City of Hope,Clinical Cancer Genomics Community Research Network (author)
Elliott, AaronAmbry Genetics Corporation (author)
Southey, MelissaUniversity of Melbourne,Monash University (author)
Winqvist, RobertUniversity of Oulu (author)
Easton, Douglas F.University of Cambridge (author)
Foulkes, William D.McGill University (author)
Antoniou, Antonis C.University of Cambridge (author)
Tischkowitz, MarcUniversity of Cambridge (author)
University of CambridgeBrigham and Women's Hospital / Harvard Medical School (creator_code:org_t)

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In:Journal of Clinical Oncology38:7, s. 674-6850732-183X

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By the author/editor: Yang, Xin; Leslie, Goska; Doroszuk, Alicja; Schneider, Sandr ...; Allen, Jamie; Decker, Brennan; show more...; Dunning, Alison ...; Redman, James; Scarth, James; Plaskocinska, In ...; Luccarini, Craig; Shah, Mitul; Pooley, Karen; Dorling, Leila; Leei, Andrew; Adank, Muriel A.; Adlard, Julian; Aittomäki, Krist ...; Andrulis, Irene ...; Ang, Peter; Barwell, Julian; Bernstein, Jonin ...; Bobolis, Kristie; Borg, Åke; Blomqvist, Carl; Claes, Kathleen ...; Concannon, Patri ...; Cuggia, Adeline; Culver, Julie O.; Damiola, Frances ...; De Pauw, Antoine; Diez, Orland; Dolinsky, Jill S ...; Domchek, Susan M ...; Engel, Christoph; Evans, D. Gareth; Fostira, Florent ...; Garber, Judy; Golmard, Lisa; Goode, Ellen L.; Gruber, Stephen ...; Hahnen, Eric; Hake, Christophe ...; Heikkinen, Tuoma ...; Hurley, Judith E ...; Janavicius, Ramu ...; Kleibl, Zdenek; Kleiblova, Petra; Konstantopoulou, ...; Kvist, Anders; Laduca, Holly; Lee, Ann S.G.; Lesueur, Fabienn ...; Maher, Eamonn R.; Mannermaa, Arto; Manoukian, Siran ...; McFarland, Rache ...; McKinnon, Wendy; Meindl, Alfons; Metcalfe, Kelly; Taib, Nur Aishah ...; Moilanen, Jukka; Nathanson, Kathe ...; Neuhausen, Susan; Ng, Pei Sze; Nguyen-Dumont, T ...; Nielsen, Sarah M ...; Obermair, Floria ...; Offit, Kenneth; Olopade, Olufunm ...; Ottini, Laura; Penkert, Judith; Pylkäs, Katri; Goldgar, David; Ramus, Susan J.; Rudaitis, Vilius; Side, Lucy; Silva-Smith, Rac ...; Silvestri, Valen ...; Skytte, Anne Bin ...; Slavin, Thomas; Soukupova, Jana; Tondini, Carlo; Trainer, Alison ...; Unzeitig, Gary; Usha, Lydia; Van Overeem Hans ...; Whitworth, James; Wood, Marie; Yip, Cheng Har; Yoon, Sook Yee; Yussuf, Amal; Zogopoulos, Geor ...; Radice, Paolo; Hopper, John L.; Chenevix-Trench, ...; Pharoah, Paul; George, Sophia H ...; Balmaña, Judith; Houdayer, Claude; James, Paul; El-Haffaf, Zaki; Ehrencrona, Hans; Janatova, Market ...; Peterlongo, Paol ...; Nevanlinna, Heli; Schmutzler, Rita; Teo, Soo Hwang; Robson, Mark; Pal, Tuya; Couch, Fergus; Weitzel, Jeffrey ...; Elliott, Aaron; Southey, Melissa; Winqvist, Robert; Easton, Douglas ...; Foulkes, William ...; Antoniou, Antoni ...; Tischkowitz, Mar ...; show less...

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