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Genome-wide association study of germline variants and breast cancer-specific mortality
Escala-Garcia, M Guo, Q Dork, T Canisius, S Keeman, R Dennis, J Beesley, J Lecarpentier, J Bolla, K Wang, Q
Escala-Garcia, M
Guo, Q
Dork, T
Canisius, S
Keeman, R
Dennis, J
Beesley, J
Lecarpentier, J
Bolla, K
Wang, Q
Citations
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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.
Authors
Escala-Garcia, M
Guo, Q
Dork, T
Canisius, S
Keeman, R
Dennis, J
Beesley, J
Lecarpentier, J
Bolla, K
Wang, Q
Abraham, J
Andrulis, L
Anton-Culver, H
Arndt, V
Auer, L
Beckmann, W
Behrens, S
Benitez, J
Bermisheva, M
Bernstein, L
Blomqvist, C
Boeckx, B
Bojesen, E
Bonanni, B
Borresen-Dale, L
Brauch, H
Brenner, H
Brentnall, A
Brinton, L
Broberg, P
Brock, W
Brucker, Y
Burwinkel, B
Caldas, C
Caldes, T
Campa, D
Canzian, F
Carracedo, A
Carter, D
Castelao, E
Chang-Claude, J
Chanock, J
Chenevix-Trench, G
Cheng, D
Chin, F
Clarke, L
Cordina-Duverger, E
Couch, J
Cox, G
Cox, A
Cross, S
Czene, K
Daly, B
Devilee, P
Dunn, A
Dunning, M
Durcan, L
Dwek, M
Earl, M
Ekici, B
Eliassen, H
Ellberg, C
Engel, C
Eriksson, M
Evans, G
Figueroa, J
Flesch-Janys, D
Flyger, H
Gabrielson, M
Gago-Dominguez, M
Galle, E
Gapstur, M
Garcia-Closas, M
Garcia-Saenz, A
Gaudet, M
George, A
Georgoulias, V
Giles, G
Glendon, G
Goldgar, E
Gonzalez-Neira, A
Alnaes, G
Grip, M
Guenel, P
Haeberle, L
Hahnen, E
Haiman, A
Hakansson, N
Hall, P
Hamann, U
Hankinson, S
Harkness, F
Harrington, A
Hart, N
Hartikainen, JM
Hein, A
Hillemanns, P
Hiller, L
Holleczek, B
Hollestelle, A
Hooning, J
Hoover, N
Hopper, L
Howell, Anthony
Huang, G
Humphreys, K
Hunter, J
Janni, W
John, M
Jones, E
Jukkola-Vuorinen, A
Jung, A
Kaaks, R
Kabisch, M
Kaczmarek, K
Kerin, J
Khan, S
Khusnutdinova, E
Kiiski, I
Kitahara, M
Knight, A
Ko, D
Koppert, B
Kosma, M
Kraft, P
Kristensen, N
Kruger, U
Kuhl, T
Lambrechts, D
Le, L
Lee, E
Lejbkowicz, F
Li, L
Lindblom, A
Lindstrom, S
Linet, M
Lissowska, J
Lo, Y
Loibl, S
Lubinski, J
Lux, P
MacInnis, J
Maierthaler, M
Maishman, T
Makalic, E
Mannermaa, A
Manoochehri, M
Manoukian, S
Margolin, S
Martinez, E
Mavroudis, D
McLean, C
Meindl, A
Middha, P
Miller, N
Milne, L
Moreno, F
Mulligan, M
Mulot, C
Nassir, R
Neuhausen, L
Newman, T
Nielsen, F
Nordestgaard, G
Norman, A
Olsson, H
Orr, N
Pankratz, S
Park-Simon, TW
Perez, A
Perez-Barrios, C
Peterlongo, P
Petridis, C
Pinchev, M
Prajzendanc, K
Prentice, R
Presneau, N
Prokofieva, D
Pylkas, K
Rack, B
Radice, P
Ramachandran, D
Rennert, G
Rennert, S
Rhenius, V
Romero, A
Roylance, R
Saloustros, E
Sawyer, J
Schmidt, DF
Schmutzler, K
Schneeweiss, A
Schoemaker, J
Schumacher, F
Schwentner, L
Scott, J
Scott, C
Seynaeve, C
Shah, M
Simard, J
Smeets, A
Sohn, C
Southey, C
Swerdlow, J
Talhouk, A
Tamimi, M
Tapper, J
Teixeira, R
Tengstrom, M
Terry, B
Thone, K
Tollenaar, M
Tomlinson, I
Torres, D
Truong, T
Turman, C
Turnbull, C
Ulmer, U
Untch, M
Vachon, C
van Asperen, J
van den Ouweland, W
van Veen, M
Wendt, C
Whittemore, S
Willett, W
Winqvist, R
Wolk, A
Yang, R
Zhang, Y
Easton, F
Fasching, A
Nevanlinna, H
Eccles, M
Pharoah, P
Schmidt, K
Guo, Q
Dork, T
Canisius, S
Keeman, R
Dennis, J
Beesley, J
Lecarpentier, J
Bolla, K
Wang, Q
Abraham, J
Andrulis, L
Anton-Culver, H
Arndt, V
Auer, L
Beckmann, W
Behrens, S
Benitez, J
Bermisheva, M
Bernstein, L
Blomqvist, C
Boeckx, B
Bojesen, E
Bonanni, B
Borresen-Dale, L
Brauch, H
Brenner, H
Brentnall, A
Brinton, L
Broberg, P
Brock, W
Brucker, Y
Burwinkel, B
Caldas, C
Caldes, T
Campa, D
Canzian, F
Carracedo, A
Carter, D
Castelao, E
Chang-Claude, J
Chanock, J
Chenevix-Trench, G
Cheng, D
Chin, F
Clarke, L
Cordina-Duverger, E
Couch, J
Cox, G
Cox, A
Cross, S
Czene, K
Daly, B
Devilee, P
Dunn, A
Dunning, M
Durcan, L
Dwek, M
Earl, M
Ekici, B
Eliassen, H
Ellberg, C
Engel, C
Eriksson, M
Evans, G
Figueroa, J
Flesch-Janys, D
Flyger, H
Gabrielson, M
Gago-Dominguez, M
Galle, E
Gapstur, M
Garcia-Closas, M
Garcia-Saenz, A
Gaudet, M
George, A
Georgoulias, V
Giles, G
Glendon, G
Goldgar, E
Gonzalez-Neira, A
Alnaes, G
Grip, M
Guenel, P
Haeberle, L
Hahnen, E
Haiman, A
Hakansson, N
Hall, P
Hamann, U
Hankinson, S
Harkness, F
Harrington, A
Hart, N
Hartikainen, JM
Hein, A
Hillemanns, P
Hiller, L
Holleczek, B
Hollestelle, A
Hooning, J
Hoover, N
Hopper, L
Howell, Anthony
Huang, G
Humphreys, K
Hunter, J
Janni, W
John, M
Jones, E
Jukkola-Vuorinen, A
Jung, A
Kaaks, R
Kabisch, M
Kaczmarek, K
Kerin, J
Khan, S
Khusnutdinova, E
Kiiski, I
Kitahara, M
Knight, A
Ko, D
Koppert, B
Kosma, M
Kraft, P
Kristensen, N
Kruger, U
Kuhl, T
Lambrechts, D
Le, L
Lee, E
Lejbkowicz, F
Li, L
Lindblom, A
Lindstrom, S
Linet, M
Lissowska, J
Lo, Y
Loibl, S
Lubinski, J
Lux, P
MacInnis, J
Maierthaler, M
Maishman, T
Makalic, E
Mannermaa, A
Manoochehri, M
Manoukian, S
Margolin, S
Martinez, E
Mavroudis, D
McLean, C
Meindl, A
Middha, P
Miller, N
Milne, L
Moreno, F
Mulligan, M
Mulot, C
Nassir, R
Neuhausen, L
Newman, T
Nielsen, F
Nordestgaard, G
Norman, A
Olsson, H
Orr, N
Pankratz, S
Park-Simon, TW
Perez, A
Perez-Barrios, C
Peterlongo, P
Petridis, C
Pinchev, M
Prajzendanc, K
Prentice, R
Presneau, N
Prokofieva, D
Pylkas, K
Rack, B
Radice, P
Ramachandran, D
Rennert, G
Rennert, S
Rhenius, V
Romero, A
Roylance, R
Saloustros, E
Sawyer, J
Schmidt, DF
Schmutzler, K
Schneeweiss, A
Schoemaker, J
Schumacher, F
Schwentner, L
Scott, J
Scott, C
Seynaeve, C
Shah, M
Simard, J
Smeets, A
Sohn, C
Southey, C
Swerdlow, J
Talhouk, A
Tamimi, M
Tapper, J
Teixeira, R
Tengstrom, M
Terry, B
Thone, K
Tollenaar, M
Tomlinson, I
Torres, D
Truong, T
Turman, C
Turnbull, C
Ulmer, U
Untch, M
Vachon, C
van Asperen, J
van den Ouweland, W
van Veen, M
Wendt, C
Whittemore, S
Willett, W
Winqvist, R
Wolk, A
Yang, R
Zhang, Y
Easton, F
Fasching, A
Nevanlinna, H
Eccles, M
Pharoah, P
Schmidt, K
Description
Date
2019
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Article
Citation
Escala-Garcia M, Guo Q, Dork T, Canisius S, Keeman R, Dennis J, et al. Genome-wide association study of germline variants and breast cancer-specific mortality. Br J Cancer. 2019 Feb 21.