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Genome-wide association study of germline variants and breast cancer-specific mortality.
- Author(s): Escala-Garcia, Maria
- Guo, Qi
- Dörk, Thilo
- Canisius, Sander
- Keeman, Renske
- Dennis, Joe
- Beesley, Jonathan
- Lecarpentier, Julie
- Bolla, Manjeet K
- Wang, Qin
- Abraham, Jean
- Andrulis, Irene L
- Anton-Culver, Hoda
- Arndt, Volker
- Auer, Paul L
- Beckmann, Matthias W
- Behrens, Sabine
- Benitez, Javier
- Bermisheva, Marina
- Bernstein, Leslie
- Blomqvist, Carl
- Boeckx, Bram
- Bojesen, Stig E
- Bonanni, Bernardo
- Børresen-Dale, Anne-Lise
- Brauch, Hiltrud
- Brenner, Hermann
- Brentnall, Adam
- Brinton, Louise
- Broberg, Per
- Brock, Ian W
- Brucker, Sara Y
- Burwinkel, Barbara
- Caldas, Carlos
- Caldés, Trinidad
- Campa, Daniele
- Canzian, Federico
- Carracedo, Angel
- Carter, Brian D
- Castelao, Jose E
- Chang-Claude, Jenny
- Chanock, Stephen J
- Chenevix-Trench, Georgia
- Cheng, Ting-Yuan David
- Chin, Suet-Feung
- Clarke, Christine L
- NBCS Collaborators
- Cordina-Duverger, Emilie
- Couch, Fergus J
- Cox, David G
- Cox, Angela
- Cross, Simon S
- Czene, Kamila
- Daly, Mary B
- Devilee, Peter
- Dunn, Janet A
- Dunning, Alison M
- Durcan, Lorraine
- Dwek, Miriam
- Earl, Helena M
- Ekici, Arif B
- Eliassen, A Heather
- Ellberg, Carolina
- Engel, Christoph
- Eriksson, Mikael
- Evans, D Gareth
- Figueroa, Jonine
- Flesch-Janys, Dieter
- Flyger, Henrik
- Gabrielson, Marike
- Gago-Dominguez, Manuela
- Galle, Eva
- Gapstur, Susan M
- García-Closas, Montserrat
- García-Sáenz, José A
- Gaudet, Mia M
- George, Angela
- Georgoulias, Vassilios
- Giles, Graham G
- Glendon, Gord
- Goldgar, David E
- González-Neira, Anna
- Alnæs, Grethe I Grenaker
- Grip, Mervi
- Guénel, Pascal
- Haeberle, Lothar
- Hahnen, Eric
- Haiman, Christopher A
- Håkansson, Niclas
- Hall, Per
- Hamann, Ute
- Hankinson, Susan
- Harkness, Elaine F
- Harrington, Patricia A
- Hart, Steven N
- Hartikainen, Jaana M
- Hein, Alexander
- Hillemanns, Peter
- Hiller, Louise
- Holleczek, Bernd
- Hollestelle, Antoinette
- Hooning, Maartje J
- Hoover, Robert N
- Hopper, John L
- Howell, Anthony
- Huang, Guanmengqian
- Humphreys, Keith
- Hunter, David J
- Janni, Wolfgang
- John, Esther M
- Jones, Michael E
- Jukkola-Vuorinen, Arja
- Jung, Audrey
- Kaaks, Rudolf
- Kabisch, Maria
- Kaczmarek, Katarzyna
- Kerin, Michael J
- Khan, Sofia
- Khusnutdinova, Elza
- Kiiski, Johanna I
- Kitahara, Cari M
- Knight, Julia A
- Ko, Yon-Dschun
- Koppert, Linetta B
- Kosma, Veli-Matti
- Kraft, Peter
- Kristensen, Vessela N
- Krüger, Ute
- Kühl, Tabea
- Lambrechts, Diether
- Le Marchand, Loic
- Lee, Eunjung
- Lejbkowicz, Flavio
- Li, Lian
- Lindblom, Annika
- Lindström, Sara
- Linet, Martha
- Lissowska, Jolanta
- Lo, Wing-Yee
- Loibl, Sibylle
- Lubiński, Jan
- Lux, Michael P
- MacInnis, Robert J
- Maierthaler, Melanie
- Maishman, Tom
- Makalic, Enes
- Mannermaa, Arto
- Manoochehri, Mehdi
- Manoukian, Siranoush
- Margolin, Sara
- Martinez, Maria Elena
- Mavroudis, Dimitrios
- McLean, Catriona
- Meindl, Alfons
- Middha, Pooja
- Miller, Nicola
- Milne, Roger L
- Moreno, Fernando
- Mulligan, Anna Marie
- Mulot, Claire
- Nassir, Rami
- Neuhausen, Susan L
- Newman, William T
- Nielsen, Sune F
- Nordestgaard, Børge G
- Norman, Aaron
- Olsson, Håkan
- Orr, Nick
- Pankratz, V Shane
- Park-Simon, Tjoung-Won
- Perez, Jose IA
- Pérez-Barrios, Clara
- Peterlongo, Paolo
- Petridis, Christos
- Pinchev, Mila
- Prajzendanc, Karoliona
- Prentice, Ross
- Presneau, Nadege
- Prokofieva, Darya
- Pylkäs, Katri
- Rack, Brigitte
- Radice, Paolo
- Ramachandran, Dhanya
- Rennert, Gadi
- Rennert, Hedy S
- Rhenius, Valerie
- Romero, Atocha
- Roylance, Rebecca
- Saloustros, Emmanouil
- Sawyer, Elinor J
- Schmidt, Daniel F
- Schmutzler, Rita K
- Schneeweiss, Andreas
- Schoemaker, Minouk J
- Schumacher, Fredrick
- Schwentner, Lukas
- Scott, Rodney J
- Scott, Christopher
- Seynaeve, Caroline
- Shah, Mitul
- Simard, Jacques
- Smeets, Ann
- Sohn, Christof
- Southey, Melissa C
- Swerdlow, Anthony J
- Talhouk, Aline
- Tamimi, Rulla M
- Tapper, William J
- Teixeira, Manuel R
- Tengström, Maria
- Terry, Mary Beth
- Thöne, Kathrin
- Tollenaar, Rob AEM
- Tomlinson, Ian
- Torres, Diana
- Truong, Thérèse
- Turman, Constance
- Turnbull, Clare
- Ulmer, Hans-Ulrich
- Untch, Michael
- Vachon, Celine
- van Asperen, Christi J
- van den Ouweland, Ans MW
- van Veen, Elke M
- Wendt, Camilla
- Whittemore, Alice S
- Willett, Walter
- Winqvist, Robert
- Wolk, Alicja
- Yang, Xiaohong R
- Zhang, Yan
- Easton, Douglas F
- Fasching, Peter A
- Nevanlinna, Heli
- Eccles, Diana M
- Pharoah, Paul DP
- Schmidt, Marjanka K
- et al.
Abstract
Background
We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.Methods
Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).Results
We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.Conclusions
We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.