The impact of coding germline variants on contralateral breast cancer risk and survival.
breast cancer susceptibility genes
coding germline variants
contralateral breast cancer risk
survival
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
02 03 2023
02 03 2023
Historique:
received:
20
07
2022
accepted:
01
02
2023
pubmed:
25
2
2023
medline:
8
3
2023
entrez:
24
2
2023
Statut:
ppublish
Résumé
Evidence linking coding germline variants in breast cancer (BC)-susceptibility genes other than BRCA1, BRCA2, and CHEK2 with contralateral breast cancer (CBC) risk and breast cancer-specific survival (BCSS) is scarce. The aim of this study was to assess the association of protein-truncating variants (PTVs) and rare missense variants (MSVs) in nine known (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53) and 25 suspected BC-susceptibility genes with CBC risk and BCSS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox regression models. Analyses included 34,401 women of European ancestry diagnosed with BC, including 676 CBCs and 3,449 BC deaths; the median follow-up was 10.9 years. Subtype analyses were based on estrogen receptor (ER) status of the first BC. Combined PTVs and pathogenic/likely pathogenic MSVs in BRCA1, BRCA2, and TP53 and PTVs in CHEK2 and PALB2 were associated with increased CBC risk [HRs (95% CIs): 2.88 (1.70-4.87), 2.31 (1.39-3.85), 8.29 (2.53-27.21), 2.25 (1.55-3.27), and 2.67 (1.33-5.35), respectively]. The strongest evidence of association with BCSS was for PTVs and pathogenic/likely pathogenic MSVs in BRCA2 (ER-positive BC) and TP53 and PTVs in CHEK2 [HRs (95% CIs): 1.53 (1.13-2.07), 2.08 (0.95-4.57), and 1.39 (1.13-1.72), respectively, after adjusting for tumor characteristics and treatment]. HRs were essentially unchanged when censoring for CBC, suggesting that these associations are not completely explained by increased CBC risk, tumor characteristics, or treatment. There was limited evidence of associations of PTVs and/or rare MSVs with CBC risk or BCSS for the 25 suspected BC genes. The CBC findings are relevant to treatment decisions, follow-up, and screening after BC diagnosis.
Identifiants
pubmed: 36827971
pii: S0002-9297(23)00047-2
doi: 10.1016/j.ajhg.2023.02.003
pmc: PMC10027471
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
475-486Subventions
Organisme : Wellcome Trust
ID : 203477/Z/16/Z
Pays : United Kingdom
Investigateurs
Kristine K Sahlberg
(KK)
Anne-Lise Børresen-Dale
(AL)
Inger Torhild Gram
(IT)
Karina Standahl Olsen
(KS)
Olav Engebråten
(O)
Bjørn Naume
(B)
Jürgen Geisler
(J)
None Osbreac
Grethe I Grenaker Alnæs
(GI)
David Amor
(D)
Lesley Andrews
(L)
Yoland Antill
(Y)
Rosemary Balleine
(R)
Jonathan Beesley
(J)
Ian Bennett
(I)
Michael Bogwitz
(M)
Leon Botes
(L)
Meagan Brennan
(M)
Melissa Brown
(M)
Michael Buckley
(M)
Jo Burke
(J)
Phyllis Butow
(P)
Liz Caldon
(L)
Ian Campbell
(I)
Michelle Cao
(M)
Anannya Chakrabarti
(A)
Deepa Chauhan
(D)
Manisha Chauhan
(M)
Georgia Chenevix-Trench
(G)
Alice Christian
(A)
Paul Cohen
(P)
Alison Colley
(A)
Ashley Crook
(A)
James Cui
(J)
Eliza Courtney
(E)
Margaret Cummings
(M)
Sarah-Jane Dawson
(SJ)
Anna DeFazio
(A)
Martin Delatycki
(M)
Rebecca Dickson
(R)
Joanne Dixon
(J)
Ted Edkins
(T)
Stacey Edwards
(S)
Gelareh Farshid
(G)
Andrew Fellows
(A)
Georgina Fenton
(G)
Michael Field
(M)
James Flanagan
(J)
Peter Fong
(P)
Laura Forrest
(L)
Stephen Fox
(S)
Juliet French
(J)
Michael Friedlander
(M)
Clara Gaff
(C)
Mike Gattas
(M)
Peter George
(P)
Sian Greening
(S)
Marion Harris
(M)
Stewart Hart
(S)
Nick Hayward
(N)
John Hopper
(J)
Cass Hoskins
(C)
Clare Hunt
(C)
Paul James
(P)
Mark Jenkins
(M)
Alexa Kidd
(A)
Judy Kirk
(J)
Jessica Koehler
(J)
James Kollias
(J)
Sunil Lakhani
(S)
Mitchell Lawrence
(M)
Jason Lee
(J)
Shuai Li
(S)
Geoff Lindeman
(G)
Lara Lipton
(L)
Liz Lobb
(L)
Sherene Loi
(S)
Graham Mann
(G)
Deborah Marsh
(D)
Sue Anne McLachlan
(SA)
Bettina Meiser
(B)
Roger Milne
(R)
Sophie Nightingale
(S)
Shona O'Connell
(S)
Sarah O'Sullivan
(S)
David Gallego Ortega
(DG)
Nick Pachter
(N)
Jia-Min Pang
(JM)
Gargi Pathak
(G)
Briony Patterson
(B)
Amy Pearn
(A)
Kelly Phillips
(K)
Ellen Pieper
(E)
Susan Ramus
(S)
Edwina Rickard
(E)
Bridget Robinson
(B)
Mona Saleh
(M)
Anita Skandarajah
(A)
Elizabeth Salisbury
(E)
Christobel Saunders
(C)
Jodi Saunus
(J)
Rodney Scott
(R)
Clare Scott
(C)
Adrienne Sexton
(A)
Andrew Shelling
(A)
Peter Simpson
(P)
Melissa Southey
(M)
Amanda Spurdle
(A)
Jessica Taylor
(J)
Renea Taylor
(R)
Heather Thorne
(H)
Alison Trainer
(A)
Kathy Tucker
(K)
Jane Visvader
(J)
Logan Walker
(L)
Rachael Williams
(R)
Ingrid Winship
(I)
Mary Ann Young
(MA)
Milita Zaheed
(M)
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests B.D. is a stockholder of Roche, Vaccitech and EQRx. P.A.F. conducts research funded by Amgen, Novartis, and Pfizer outside the submitted work. He received honoraria from Roche, Novartis, and Pfizer outside the submitted work. D.F.E. is an associate editor at The American Journal of Human Genetics (AJHG).
Références
Cancer. 2000 Jun 15;88(12):2739-50
pubmed: 10870056
Breast Cancer Res. 2018 Jan 24;20(1):7
pubmed: 29368626
Genet Med. 2019 Aug;21(8):1708-1718
pubmed: 30643217
J Natl Cancer Inst. 2017 Aug 1;109(8):
pubmed: 28376189
N Engl J Med. 2021 Feb 4;384(5):428-439
pubmed: 33471991
Br J Cancer. 2000 Aug;83(3):384-6
pubmed: 10917555
NPJ Breast Cancer. 2019 Oct 29;5:37
pubmed: 31700993
Radiother Oncol. 2007 Mar;82(3):349-53
pubmed: 17250914
Breast Cancer Res Treat. 2021 Aug;188(3):821-823
pubmed: 34132937
N Engl J Med. 2015 Jun 4;372(23):2243-57
pubmed: 26014596
Breast. 2021 Apr;56:61-69
pubmed: 33621798
Clin Cancer Res. 2009 May 1;15(9):3214-22
pubmed: 19383810
Nature. 2017 Nov 2;551(7678):92-94
pubmed: 29059683
Lancet Oncol. 2018 Feb;19(2):169-180
pubmed: 29337092
JAMA. 2011 Feb 23;305(8):822-3
pubmed: 21343582
Clin Breast Cancer. 2021 Feb;21(1):e63-e73
pubmed: 32893093
Int J Womens Health. 2016 Jun 22;8:213-23
pubmed: 27382334
Semin Cancer Biol. 2021 Jul;72:76-89
pubmed: 31881337
Breast Cancer Res Treat. 2011 Nov;130(2):609-18
pubmed: 21671018
Cancers (Basel). 2019 May 28;11(6):
pubmed: 31141992
Ann Surg Oncol. 2015 Dec;22 Suppl 3:S412-21
pubmed: 26334294
Lancet Oncol. 2015 Jun;16(6):638-44
pubmed: 25959805
J Natl Cancer Inst. 2019 Jul 1;111(7):709-718
pubmed: 30698719
JAMA. 2017 Jun 20;317(23):2402-2416
pubmed: 28632866
J Clin Oncol. 2012 Dec 10;30(35):4308-16
pubmed: 23109706
Ann Surg. 2017 Mar;265(3):581-589
pubmed: 28169929
Int J Cancer. 2020 Feb 15;146(4):999-1009
pubmed: 31081934
J Clin Oncol. 2007 Sep 20;25(27):4210-6
pubmed: 17878475
Cancers (Basel). 2020 Feb 07;12(2):
pubmed: 32045981
Front Immunol. 2019 Mar 01;10:348
pubmed: 30881360
J Clin Oncol. 2016 Feb 10;34(5):409-18
pubmed: 26700119
Cancer Epidemiol. 2016 Jun;42:24-31
pubmed: 26999400
N Engl J Med. 2021 Feb 4;384(5):440-451
pubmed: 33471974
PLoS One. 2015 Mar 27;10(3):e0120189
pubmed: 25816289
J Med Genet. 2019 Jun;56(6):347-357
pubmed: 30962250
J Clin Epidemiol. 2013 Feb;66(2):192-6
pubmed: 23257150
J Clin Oncol. 2007 Jan 1;25(1):64-9
pubmed: 17132695
Br J Cancer. 2019 Mar;120(6):647-657
pubmed: 30787463
Int J Cancer. 2018 Oct 15;143(8):1935-1942
pubmed: 29726012
World J Surg. 2001 Sep;25(9):1117-24
pubmed: 11571945
J Clin Oncol. 2010 May 10;28(14):2404-10
pubmed: 20368571
J Clin Oncol. 2009 Dec 10;27(35):5887-92
pubmed: 19858402
J Natl Cancer Inst. 2020 Dec 14;112(12):1275-1279
pubmed: 32119081
J Med Genet. 2011 Jul;48(7):477-84
pubmed: 21632523
J Natl Cancer Inst. 2020 Dec 14;112(12):1231-1241
pubmed: 32091585