A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
View/ Open
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 < 10-8, 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.
Collections
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
Aetiological Epidemiology
Language
eng
Date accepted
2020-11-19
License start date
2021-02-17
Citation
Nature communications, 2021, 12 (1), pp. 1078 - ?
Publisher
NATURE PORTFOLIO
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
Related items
Showing items related by title, author, creator and subject.
-
Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.
Barnes, DR; Rookus, MA; McGuffog, L; Leslie, G; Mooij, TM; et al. (ELSEVIER SCIENCE INC, 2020-10-01)PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: ... -
Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.
Feng, H; Gusev, A; Pasaniuc, B; Wu, L; Long, J; et al. (WILEY, 2020-07-01)Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer ... -
No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.
Easton, DF; Lesueur, F; Decker, B; Michailidou, K; Li, J; et al. (BMJ PUBLISHING GROUP, 2016-05-01)BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, ...