Skip to main content
Download PDF
- Main
Genome-wide association study of germline variants and breast cancer-specific mortality.
- 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.