Two truncating variants in FANCC and breast cancer risk.
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Date
2019-08-29ICR Author
Author
Dörk, T
Peterlongo, P
Mannermaa, A
Bolla, MK
Wang, Q
Dennis, J
Ahearn, T
Andrulis, IL
Anton-Culver, H
Arndt, V
Aronson, KJ
Augustinsson, A
Freeman, LEB
Beckmann, MW
Beeghly-Fadiel, A
Behrens, S
Bermisheva, M
Blomqvist, C
Bogdanova, NV
Bojesen, SE
Brauch, H
Brenner, H
Burwinkel, B
Canzian, F
Chan, TL
Chang-Claude, J
Chanock, SJ
Choi, J-Y
Christiansen, H
Clarke, CL
Couch, FJ
Czene, K
Daly, MB
Dos-Santos-Silva, I
Dwek, M
Eccles, DM
Ekici, AB
Eriksson, M
Evans, DG
Fasching, PA
Figueroa, J
Flyger, H
Fritschi, L
Gabrielson, M
Gago-Dominguez, M
Gao, C
Gapstur, SM
García-Closas, M
García-Sáenz, JA
Gaudet, MM
Giles, GG
Goldberg, MS
Goldgar, DE
Guénel, P
Haeberle, L
Haiman, CA
Håkansson, N
Hall, P
Hamann, U
Hartman, M
Hauke, J
Hein, A
Hillemanns, P
Hogervorst, FBL
Hooning, MJ
Hopper, JL
Howell, T
Huo, D
Ito, H
Iwasaki, M
Jakubowska, A
Janni, W
John, EM
Jung, A
Kaaks, R
Kang, D
Kapoor, PM
Khusnutdinova, E
Kim, S-W
Kitahara, CM
Koutros, S
Kraft, P
Kristensen, VN
Kwong, A
Lambrechts, D
Marchand, LL
Li, J
Lindström, S
Linet, M
Lo, W-Y
Long, J
Lophatananon, A
Lubiński, J
Manoochehri, M
Manoukian, S
Margolin, S
Martinez, E
Matsuo, K
Mavroudis, D
Meindl, A
Menon, U
Milne, RL
Mohd Taib, NA
Muir, K
Mulligan, AM
Neuhausen, SL
Nevanlinna, H
Neven, P
Newman, WG
Offit, K
Olopade, OI
Olshan, AF
Olson, JE
Olsson, H
Park, SK
Park-Simon, T-W
Peto, J
Plaseska-Karanfilska, D
Pohl-Rescigno, E
Presneau, N
Rack, B
Radice, P
Rashid, MU
Rennert, G
Rennert, HS
Romero, A
Ruebner, M
Saloustros, E
Schmidt, MK
Schmutzler, RK
Schneider, MO
Schoemaker, MJ
Scott, C
Shen, C-Y
Shu, X-O
Simard, J
Slager, S
Smichkoska, S
Southey, MC
Spinelli, JJ
Stone, J
Surowy, H
Swerdlow, AJ
Tamimi, RM
Tapper, WJ
Teo, SH
Terry, MB
Toland, AE
Tollenaar, RAEM
Torres, D
Torres-Mejía, G
Troester, MA
Truong, T
Tsugane, S
Untch, M
Vachon, CM
Ouweland, AMWVD
Veen, EMV
Vijai, J
Wendt, C
Wolk, A
Yu, J-C
Zheng, W
Ziogas, A
Ziv, E
ABCTB Investigators,
NBCS Collaborators,
Dunning, AM
Pharoah, PDP
Schindler, D
Devilee, P
Easton, DF
Type
Journal Article
Metadata
Show full item recordAbstract
Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
Collections
Subject
ABCTB Investigators
NBCS Collaborators
Humans
Breast Neoplasms
Fanconi Anemia
Genetic Predisposition to Disease
BRCA1 Protein
BRCA2 Protein
Case-Control Studies
Sequence Deletion
Female
Fanconi Anemia Complementation Group C Protein
Genetic Variation
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2019-08-09
License start date
2019-08-29
Citation
Scientific reports, 2019, 9 (1), pp. 12524 - ?
Publisher
NATURE PUBLISHING GROUP