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@ARTICLE{Morra:274170,
author = {A. Morra and N. Mavaddat and T. A. Muranen and T. U. Ahearn
and J. Allen and I. L. Andrulis and P. Auvinen and H. Becher
and S. Behrens$^*$ and C. Blomqvist and S. E. Bojesen and M.
K. Bolla and H. Brauch$^*$ and N. J. Camp and S. Carvalho
and J. E. Castelao and M. H. Cessna and J. Chang-Claude$^*$
and G. Chenevix-Trench and K. Czene and B. Decker and J.
Dennis and T. Dörk and L. Dorling and A. M. Dunning and A.
B. Ekici and M. Eriksson and D. G. Evans and P. A. Fasching
and J. D. Figueroa and H. Flyger and M. Gago-Dominguez and
M. García-Closas and W. R. R. Geurts-Giele and G. G. Giles
and P. Guénel and M. Gündert$^*$ and E. Hahnen and P. Hall
and U. Hamann$^*$ and P. A. Harrington and W. He and P.
Heikkilä and M. J. Hooning and R. Hoppe and A. Howell and
K. Humphreys and A. Jakubowska and A. Y. Jung$^*$ and R.
Keeman and V. N. Kristensen and J. Lubiński and A.
Mannermaa and M. Manoochehri$^*$ and S. Manoukian and S.
Margolin and D. Mavroudis and R. L. Milne and A. M. Mulligan
and W. G. Newman and T.-W. Park-Simon and P. Peterlongo and
P. D. P. Pharoah and V. Rhenius and E. Saloustros and E. J.
Sawyer and R. K. Schmutzler and M. Shah and A. B. Spurdle
and I. Tomlinson and T. Truong and E. M. van Veen and M. P.
G. Vreeswijk and Q. Wang and C. Wendt and X. R. Yang and H.
Nevanlinna and P. Devilee and D. F. Easton and M. K.
Schmidt},
collaboration = {NBCS Collaborators and k. Investigators},
othercontributors = {K. K. Sahlberg and A.-L. Børresen-Dale and I. T. Gram and
K. S. Olsen and O. Engebråten and B. Naume and J. Geisler
and Osbreac and G. I. Grenaker Alnæs and D. Amor and L.
Andrews and Y. Antill and R. Balleine and J. Beesley and I.
Bennett and M. Bogwitz and L. Botes and M. Brennan and M.
Brown and M. Buckley and J. Burke and P. Butow and L. Caldon
and I. Campbell and M. Cao and A. Chakrabarti and D. Chauhan
and M. Chauhan and G. Chenevix-Trench and A. Christian and
P. Cohen and A. Colley and A. Crook and J. Cui and E.
Courtney and M. Cummings and S.-J. Dawson and A. DeFazio and
M. Delatycki and R. Dickson and J. Dixon and T. Edkins and
S. Edwards and G. Farshid and A. Fellows and G. Fenton and
M. Field and J. Flanagan and P. Fong and L. Forrest and S.
Fox and J. French and M. Friedlander and C. Gaff and M.
Gattas and P. George and S. Greening and M. Harris and S.
Hart and N. Hayward and J. Hopper and C. Hoskins and C. Hunt
and P. James and M. Jenkins and A. Kidd and J. Kirk and J.
Koehler and J. Kollias and S. Lakhani and M. Lawrence and J.
Lee and S. Li and G. Lindeman and L. Lipton and L. Lobb and
S. Loi and G. Mann and D. Marsh and S. A. McLachlan and B.
Meiser and R. Milne and S. Nightingale and S. O'Connell and
S. O'Sullivan and D. G. Ortega and N. Pachter and J.-M. Pang
and G. Pathak and B. Patterson and A. Pearn and K. Phillips
and E. Pieper and S. Ramus and E. Rickard and B. Robinson
and M. Saleh and A. Skandarajah and E. Salisbury and C.
Saunders and J. Saunus and R. Scott and C. Scott and A.
Sexton and A. Shelling and P. Simpson and M. Southey and A.
Spurdle and J. Taylor and R. Taylor and H. Thorne and A.
Trainer and K. Tucker and J. Visvader and L. Walker and R.
Williams and I. Winship and M. A. Young and M. Zaheed},
title = {{T}he impact of coding germline variants on contralateral
breast cancer risk and survival.},
journal = {The American journal of human genetics},
volume = {110},
number = {3},
issn = {0002-9297},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2023-00472},
pages = {475 - 486},
year = {2023},
abstract = {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.},
keywords = {Female / Humans / Breast Neoplasms: genetics / Genes, BRCA2
/ Germ-Line Mutation / Germ Cells / Genetic Predisposition
to Disease / breast cancer susceptibility genes (Other) /
coding germline variants (Other) / contralateral breast
cancer risk (Other) / survival (Other)},
cin = {C020 / C080 / B072 / B070 / TU01},
ddc = {570},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)C080-20160331 /
I:(DE-He78)B072-20160331 / I:(DE-He78)B070-20160331 /
I:(DE-He78)TU01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36827971},
doi = {10.1016/j.ajhg.2023.02.003},
url = {https://inrepo02.dkfz.de/record/274170},
}