Journal Article

DKFZ-2023-00472

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The impact of coding germline variants on contralateral breast cancer risk and survival.

Morra, A. ; Mavaddat, N. ; Muranen, T. A. ; Ahearn, T. U. ; Allen, J. ; Andrulis, I. L. ; Auvinen, P. ; Becher, H. ; Behrens, S.DKFZ* ; Blomqvist, C. ; Bojesen, S. E. ; Bolla, M. K. ; Brauch, H.DKFZ* ; Camp, N. J. ; Carvalho, S. ; Castelao, J. E. ; Cessna, M. H. ; Chang-Claude, J.DKFZ* ; Chenevix-Trench, G. ; NBCS Collaborators (Collaboration Author) ; Czene, K. ; Decker, B. ; Dennis, J. ; Dörk, T. ; Dorling, L. ; Dunning, A. M. ; Ekici, A. B. ; Eriksson, M. ; Evans, D. G. ; Fasching, P. A. ; Figueroa, J. D. ; Flyger, H. ; Gago-Dominguez, M. ; García-Closas, M. ; Geurts-Giele, W. R. R. ; Giles, G. G. ; Guénel, P. ; Gündert, M.DKFZ* ; Hahnen, E. ; Hall, P. ; Hamann, U.DKFZ* ; Harrington, P. A. ; He, W. ; Heikkilä, P. ; Hooning, M. J. ; Hoppe, R. ; Howell, A. ; Humphreys, K. ; Investigators, k. (Collaboration Author) ; Jakubowska, A. ; Jung, A. Y.DKFZ* ; Keeman, R. ; Kristensen, V. N. ; Lubiński, J. ; Mannermaa, A. ; Manoochehri, M.DKFZ* ; Manoukian, S. ; Margolin, S. ; Mavroudis, D. ; Milne, R. L. ; Mulligan, A. M. ; Newman, W. G. ; Park-Simon, T.-W. ; Peterlongo, P. ; Pharoah, P. D. P. ; Rhenius, V. ; Saloustros, E. ; Sawyer, E. J. ; Schmutzler, R. K. ; Shah, M. ; Spurdle, A. B. ; Tomlinson, I. ; Truong, T. ; van Veen, E. M. ; Vreeswijk, M. P. G. ; Wang, Q. ; Wendt, C. ; Yang, X. R. ; Nevanlinna, H. ; Devilee, P. ; Easton, D. F. ; Schmidt, M. K. ; Sahlberg, K. K. (Contributor) ; Børresen-Dale, A.-L. (Contributor) ; Gram, I. T. (Contributor) ; Olsen, K. S. (Contributor) ; Engebråten, O. (Contributor) ; Naume, B. (Contributor) ; Geisler, J. (Contributor) ; Osbreac (Contributor) ; Grenaker Alnæs, G. I. (Contributor) ; Amor, D. (Contributor) ; Andrews, L. (Contributor) ; Antill, Y. (Contributor) ; Balleine, R. (Contributor) ; Beesley, J. (Contributor) ; Bennett, I. (Contributor) ; Bogwitz, M. (Contributor) ; Botes, L. (Contributor) ; Brennan, M. (Contributor) ; Brown, M. (Contributor) ; Buckley, M. (Contributor) ; Burke, J. (Contributor) ; Butow, P. (Contributor) ; Caldon, L. (Contributor) ; Campbell, I. (Contributor) ; Cao, M. (Contributor) ; Chakrabarti, A. (Contributor) ; Chauhan, D. (Contributor) ; Chauhan, M. (Contributor) ; Chenevix-Trench, G. (Contributor) ; Christian, A. (Contributor) ; Cohen, P. (Contributor) ; Colley, A. (Contributor) ; Crook, A. (Contributor) ; Cui, J. (Contributor) ; Courtney, E. (Contributor) ; Cummings, M. (Contributor) ; Dawson, S.-J. (Contributor) ; DeFazio, A. (Contributor) ; Delatycki, M. (Contributor) ; Dickson, R. (Contributor) ; Dixon, J. (Contributor) ; Edkins, T. (Contributor) ; Edwards, S. (Contributor) ; Farshid, G. (Contributor) ; Fellows, A. (Contributor) ; Fenton, G. (Contributor) ; Field, M. (Contributor) ; Flanagan, J. (Contributor) ; Fong, P. (Contributor) ; Forrest, L. (Contributor) ; Fox, S. (Contributor) ; French, J. (Contributor) ; Friedlander, M. (Contributor) ; Gaff, C. (Contributor) ; Gattas, M. (Contributor) ; George, P. (Contributor) ; Greening, S. (Contributor) ; Harris, M. (Contributor) ; Hart, S. (Contributor) ; Hayward, N. (Contributor) ; Hopper, J. (Contributor) ; Hoskins, C. (Contributor) ; Hunt, C. (Contributor) ; James, P. (Contributor) ; Jenkins, M. (Contributor) ; Kidd, A. (Contributor) ; Kirk, J. (Contributor) ; Koehler, J. (Contributor) ; Kollias, J. (Contributor) ; Lakhani, S. (Contributor) ; Lawrence, M. (Contributor) ; Lee, J. (Contributor) ; Li, S. (Contributor) ; Lindeman, G. (Contributor) ; Lipton, L. (Contributor) ; Lobb, L. (Contributor) ; Loi, S. (Contributor) ; Mann, G. (Contributor) ; Marsh, D. (Contributor) ; McLachlan, S. A. (Contributor) ; Meiser, B. (Contributor) ; Milne, R. (Contributor) ; Nightingale, S. (Contributor) ; O'Connell, S. (Contributor) ; O'Sullivan, S. (Contributor) ; Ortega, D. G. (Contributor) ; Pachter, N. (Contributor) ; Pang, J.-M. (Contributor) ; Pathak, G. (Contributor) ; Patterson, B. (Contributor) ; Pearn, A. (Contributor) ; Phillips, K. (Contributor) ; Pieper, E. (Contributor) ; Ramus, S. (Contributor) ; Rickard, E. (Contributor) ; Robinson, B. (Contributor) ; Saleh, M. (Contributor) ; Skandarajah, A. (Contributor) ; Salisbury, E. (Contributor) ; Saunders, C. (Contributor) ; Saunus, J. (Contributor) ; Scott, R. (Contributor) ; Scott, C. (Contributor) ; Sexton, A. (Contributor) ; Shelling, A. (Contributor) ; Simpson, P. (Contributor) ; Southey, M. (Contributor) ; Spurdle, A. (Contributor) ; Taylor, J. (Contributor) ; Taylor, R. (Contributor) ; Thorne, H. (Contributor) ; Trainer, A. (Contributor) ; Tucker, K. (Contributor) ; Visvader, J. (Contributor) ; Walker, L. (Contributor) ; Williams, R. (Contributor) ; Winship, I. (Contributor) ; Young, M. A. (Contributor) ; Zaheed, M. (Contributor)

2023
Elsevier New York, NY

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.ajhg.2023.02.003

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.

Keyword(s): Female (MeSH) ; Humans (MeSH) ; Breast Neoplasms: genetics (MeSH) ; Genes, BRCA2 (MeSH) ; Germ-Line Mutation (MeSH) ; Germ Cells (MeSH) ; Genetic Predisposition to Disease (MeSH) ; breast cancer susceptibility genes ; coding germline variants ; contralateral breast cancer risk ; survival

---

Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. Molekulare Epidemiologie (C080)
3. Molekulargenetik des Mammakarzinoms (B072)
4. B070 Funktionelle Genomanalyse (B070)
5. DKTK Koordinierungsstelle Tübingen (TU01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---