FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
15
07
2022
accepted:
24
11
2022
revised:
11
11
2022
medline:
12
5
2023
pubmed:
28
1
2023
entrez:
27
1
2023
Statut:
ppublish
Résumé
Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07-2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08-1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs.
Identifiants
pubmed: 36707629
doi: 10.1038/s41431-022-01257-w
pii: 10.1038/s41431-022-01257-w
pmc: PMC10172381
doi:
Substances chimiques
FANCM protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
578-587Subventions
Organisme : Wellcome Trust
ID : 203477/Z/16/Z
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA042014
Pays : United States
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)
Tone F Bathen
(TF)
Elin Borgen
(E)
Britt Fritzman
(B)
Øystein Garred
(Ø)
Gry Aarum Geitvik
(GA)
Solveig Hofvind
(S)
Anita Langerød
(A)
Ole Christian Lingjærde
(OC)
Gunhild Mari Mælandsmo
(GM)
Hege G Russnes
(HG)
Helle Kristine Skjerven
(HK)
Therese Sørlie
(T)
Grethe I Grenaker Alnæs
(GIG)
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)
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
© 2023. The Author(s).
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