A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
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Publication Date
2021-02-17ICR Author
Author
Coignard, J
Lush, M
Beesley, J
O'Mara, TA
Dennis, J
Tyrer, JP
Barnes, DR
McGuffog, L
Leslie, G
Bolla, MK
Adank, MA
Agata, S
Ahearn, T
Aittomäki, K
Andrulis, IL
Anton-Culver, H
Arndt, V
Arnold, N
Aronson, KJ
Arun, BK
Augustinsson, A
Azzollini, J
Barrowdale, D
Baynes, C
Becher, H
Bermisheva, M
Bernstein, L
Białkowska, K
Blomqvist, C
Bojesen, SE
Bonanni, B
Borg, A
Brauch, H
Brenner, H
Burwinkel, B
Buys, SS
Caldés, T
Caligo, MA
Campa, D
Carter, BD
Castelao, JE
Chang-Claude, J
Chanock, SJ
Chung, WK
Claes, KBM
Clarke, CL
GEMO Study Collaborators
EMBRACE Collaborators
Collée, JM
Conroy, DM
Czene, K
Daly, MB
Devilee, P
Diez, O
Ding, YC
Domchek, SM
Dörk, T
Dos-Santos-Silva, I
Dunning, AM
Dwek, M
Eccles, DM
Eliassen, AH
Engel, C
Eriksson, M
Evans, DG
Fasching, PA
Flyger, H
Fostira, F
Friedman, E
Fritschi, L
Frost, D
Gago-Dominguez, M
Gapstur, SM
Garber, J
Garcia-Barberan, V
García-Closas, M
García-Sáenz, JA
Gaudet, MM
Gayther, SA
Gehrig, A
Georgoulias, V
Giles, GG
Godwin, AK
Goldberg, MS
Goldgar, DE
González-Neira, A
Greene, MH
Guénel, P
Haeberle, L
Hahnen, E
Haiman, CA
Håkansson, N
Hall, P
Hamann, U
Harrington, PA
Hart, SN
He, W
Hogervorst, FBL
Hollestelle, A
Hopper, JL
Horcasitas, DJ
Hulick, PJ
Hunter, DJ
Imyanitov, EN
KConFab Investigators
HEBON Investigators
ABCTB Investigators
Jager, A
Jakubowska, A
James, PA
Jensen, UB
John, EM
Jones, ME
Kaaks, R
Kapoor, PM
Karlan, BY
Keeman, R
Khusnutdinova, E
Kiiski, JI
Ko, Y-D
Kosma, V-M
Kraft, P
Kurian, AW
Laitman, Y
Lambrechts, D
Le Marchand, L
Lester, J
Lesueur, F
Lindstrom, T
Lopez-Fernández, A
Loud, JT
Luccarini, C
Mannermaa, A
Manoukian, S
Margolin, S
Martens, JWM
Mebirouk, N
Meindl, A
Miller, A
Milne, RL
Montagna, M
Nathanson, KL
Neuhausen, SL
Nevanlinna, H
Nielsen, FC
O'Brien, KM
Olopade, OI
Olson, JE
Olsson, H
Osorio, A
Ottini, L
Park-Simon, T-W
Parsons, MT
Pedersen, IS
Peshkin, B
Peterlongo, P
Peto, J
Pharoah, PDP
Phillips, K-A
Polley, EC
Poppe, B
Presneau, N
Pujana, MA
Punie, K
Radice, P
Rantala, J
Rashid, MU
Rennert, G
Rennert, HS
Robson, M
Romero, A
Rossing, M
Saloustros, E
Sandler, DP
Santella, R
Scheuner, MT
Schmidt, MK
Schmidt, G
Scott, C
Sharma, P
Soucy, P
Southey, MC
Spinelli, JJ
Steinsnyder, Z
Stone, J
Stoppa-Lyonnet, D
Swerdlow, A
Tamimi, RM
Tapper, WJ
Taylor, JA
Terry, MB
Teulé, A
Thull, DL
Tischkowitz, M
Toland, AE
Torres, D
Trainer, AH
Truong, T
Tung, N
Vachon, CM
Vega, A
Vijai, J
Wang, Q
Wappenschmidt, B
Weinberg, CR
Weitzel, JN
Wendt, C
Wolk, A
Yadav, S
Yang, XR
Yannoukakos, D
Zheng, W
Ziogas, A
Zorn, KK
Park, SK
Thomassen, M
Offit, K
Schmutzler, RK
Couch, FJ
Simard, J
Chenevix-Trench, G
Easton, DF
Andrieu, N
Antoniou, AC
Type
Journal Article
Metadata
Show full item recordAbstract
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10<sup>-8</sup>, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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Licenseref URL
http://creativecommons.org/licenses/by/4.0/Version
VoR
Version of record
Subject
GEMO Study Collaborators
EMBRACE Collaborators
KConFab Investigators
HEBON Investigators
ABCTB Investigators
Humans
Breast Neoplasms
Genetic Predisposition to Disease
BRCA1 Protein
BRCA2 Protein
Risk Factors
Genotype
Linkage Disequilibrium
Mutation
Polymorphism, Single Nucleotide
Alleles
Quantitative Trait Loci
Adult
Middle Aged
Female
Genome-Wide Association Study
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2020-11-19
License start date
2021-02-17
Citation
Nature communications, 2021, 12 (1), pp. 1078 - ?
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
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Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.
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