No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.
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ICR Authors
Authors
Easton, DF
Lesueur, F
Decker, B
Michailidou, K
Li, J
Allen, J
Luccarini, C
Pooley, KA
Shah, M
Bolla, MK
Wang, Q
Dennis, J
Ahmad, J
Thompson, ER
Damiola, F
Pertesi, M
Voegele, C
Mebirouk, N
Robinot, N
Durand, G
Forey, N
Luben, RN
Ahmed, S
Aittomäki, K
Anton-Culver, H
Arndt, V
Australian Ovarian Cancer Study Group,
Baynes, C
Beckman, MW
Benitez, J
Van Den Berg, D
Blot, WJ
Bogdanova, NV
Bojesen, SE
Brenner, H
Chang-Claude, J
Chia, KS
Choi, J-Y
Conroy, DM
Cox, A
Cross, SS
Czene, K
Darabi, H
Devilee, P
Eriksson, M
Fasching, PA
Figueroa, J
Flyger, H
Fostira, F
García-Closas, M
Giles, GG
Glendon, G
González-Neira, A
Guénel, P
Haiman, CA
Hall, P
Hart, SN
Hartman, M
Hooning, MJ
Hsiung, C-N
Ito, H
Jakubowska, A
James, PA
John, EM
Johnson, N
Jones, M
Kabisch, M
Kang, D
kConFab Investigators,
Kosma, V-M
Kristensen, V
Lambrechts, D
Li, N
Lifepool Investigators,
Lindblom, A
Long, J
Lophatananon, A
Lubinski, J
Mannermaa, A
Manoukian, S
Margolin, S
Matsuo, K
Meindl, A
Mitchell, G
Muir, K
NBCS Investigators,
Nevelsteen, I
van den Ouweland, A
Peterlongo, P
Phuah, SY
Pylkäs, K
Rowley, SM
Sangrajrang, S
Schmutzler, RK
Shen, C-Y
Shu, X-O
Southey, MC
Surowy, H
Swerdlow, A
Teo, SH
Tollenaar, RAEM
Tomlinson, I
Torres, D
Truong, T
Vachon, C
Verhoef, S
Wong-Brown, M
Zheng, W
Zheng, Y
Nevanlinna, H
Scott, RJ
Andrulis, IL
Wu, AH
Hopper, JL
Couch, FJ
Winqvist, R
Burwinkel, B
Sawyer, EJ
Schmidt, MK
Rudolph, A
Dörk, T
Brauch, H
Hamann, U
Neuhausen, SL
Milne, RL
Fletcher, O
Pharoah, PDP
Campbell, IG
Dunning, AM
Le Calvez-Kelm, F
Goldgar, DE
Tavtigian, SV
Chenevix-Trench, G
Lesueur, F
Decker, B
Michailidou, K
Li, J
Allen, J
Luccarini, C
Pooley, KA
Shah, M
Bolla, MK
Wang, Q
Dennis, J
Ahmad, J
Thompson, ER
Damiola, F
Pertesi, M
Voegele, C
Mebirouk, N
Robinot, N
Durand, G
Forey, N
Luben, RN
Ahmed, S
Aittomäki, K
Anton-Culver, H
Arndt, V
Australian Ovarian Cancer Study Group,
Baynes, C
Beckman, MW
Benitez, J
Van Den Berg, D
Blot, WJ
Bogdanova, NV
Bojesen, SE
Brenner, H
Chang-Claude, J
Chia, KS
Choi, J-Y
Conroy, DM
Cox, A
Cross, SS
Czene, K
Darabi, H
Devilee, P
Eriksson, M
Fasching, PA
Figueroa, J
Flyger, H
Fostira, F
García-Closas, M
Giles, GG
Glendon, G
González-Neira, A
Guénel, P
Haiman, CA
Hall, P
Hart, SN
Hartman, M
Hooning, MJ
Hsiung, C-N
Ito, H
Jakubowska, A
James, PA
John, EM
Johnson, N
Jones, M
Kabisch, M
Kang, D
kConFab Investigators,
Kosma, V-M
Kristensen, V
Lambrechts, D
Li, N
Lifepool Investigators,
Lindblom, A
Long, J
Lophatananon, A
Lubinski, J
Mannermaa, A
Manoukian, S
Margolin, S
Matsuo, K
Meindl, A
Mitchell, G
Muir, K
NBCS Investigators,
Nevelsteen, I
van den Ouweland, A
Peterlongo, P
Phuah, SY
Pylkäs, K
Rowley, SM
Sangrajrang, S
Schmutzler, RK
Shen, C-Y
Shu, X-O
Southey, MC
Surowy, H
Swerdlow, A
Teo, SH
Tollenaar, RAEM
Tomlinson, I
Torres, D
Truong, T
Vachon, C
Verhoef, S
Wong-Brown, M
Zheng, W
Zheng, Y
Nevanlinna, H
Scott, RJ
Andrulis, IL
Wu, AH
Hopper, JL
Couch, FJ
Winqvist, R
Burwinkel, B
Sawyer, EJ
Schmidt, MK
Rudolph, A
Dörk, T
Brauch, H
Hamann, U
Neuhausen, SL
Milne, RL
Fletcher, O
Pharoah, PDP
Campbell, IG
Dunning, AM
Le Calvez-Kelm, F
Goldgar, DE
Tavtigian, SV
Chenevix-Trench, G
Document Type
Journal Article
Date
2016-05-01
Date Accepted
2015-12-16
Abstract
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, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.
Citation
Journal of medical genetics, 2016, 53 (5), pp. 298 - 309
Source Title
Publisher
BMJ PUBLISHING GROUP
ISSN
0022-2593
eISSN
1468-6244
Research Team
Functional Genetic Epidemiology
Aetiological Epidemiology
Aetiological Epidemiology