No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.
View/ Open
Date
2016-05-01Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Australian Ovarian Cancer Study Group
kConFab Investigators
Lifepool Investigators
NBCS Investigators
Humans
Breast Neoplasms
Genetic Predisposition to Disease
RNA Helicases
DNA-Binding Proteins
Risk
Cohort Studies
Mutation
Adult
Aged
Middle Aged
European Continental Ancestry Group
Female
Fanconi Anemia Complementation Group Proteins
Genetic Association Studies
Research team
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2015-12-16
License start date
2016-05
Citation
Journal of medical genetics, 2016, 53 (5), pp. 298 - 309
Publisher
BMJ PUBLISHING GROUP
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 ... -
The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.
Lakeman, IMM; van den Broek, AJ; Vos, JAM; Barnes, DR; Adlard, J; et al. (ELSEVIER SCIENCE INC, 2021-06-10)PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant ...