No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing
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No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk : implications for gene panel testing. / Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen A; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Ahmad, Jamil; Thompson, Ella R; Damiola, Francesca; Pertesi, Maroulio; Voegele, Catherine; Mebirouk, Noura; Robinot, Nivonirina; Durand, Geoffroy; Forey, Nathalie; Luben, Robert N; Ahmed, Shahana; Aittomäki, Kristiina; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Beckman, Matthias W; Benitez, Javier; Van Den Berg, David; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Brenner, Hermann; Chang-Claude, Jenny; Chia, Kee Seng; Choi, Ji-Yeob; Conroy, Don M; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Fostira, Florentia; García-Closas, Montserrat; Giles, Graham G; Australian Ovarian Cancer Study Group.
In: Journal of Medical Genetics, Vol. 53, 05.2016, p. 298-309.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk
T2 - implications for gene panel testing
AU - Easton, Douglas F
AU - Lesueur, Fabienne
AU - Decker, Brennan
AU - Michailidou, Kyriaki
AU - Li, Jun
AU - Allen, Jamie
AU - Luccarini, Craig
AU - Pooley, Karen A
AU - Shah, Mitul
AU - Bolla, Manjeet K
AU - Wang, Qin
AU - Dennis, Joe
AU - Ahmad, Jamil
AU - Thompson, Ella R
AU - Damiola, Francesca
AU - Pertesi, Maroulio
AU - Voegele, Catherine
AU - Mebirouk, Noura
AU - Robinot, Nivonirina
AU - Durand, Geoffroy
AU - Forey, Nathalie
AU - Luben, Robert N
AU - Ahmed, Shahana
AU - Aittomäki, Kristiina
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Baynes, Caroline
AU - Beckman, Matthias W
AU - Benitez, Javier
AU - Van Den Berg, David
AU - Blot, William J
AU - Bogdanova, Natalia V
AU - Bojesen, Stig E
AU - Brenner, Hermann
AU - Chang-Claude, Jenny
AU - Chia, Kee Seng
AU - Choi, Ji-Yeob
AU - Conroy, Don M
AU - Cox, Angela
AU - Cross, Simon S
AU - Czene, Kamila
AU - Darabi, Hatef
AU - Devilee, Peter
AU - Eriksson, Mikael
AU - Fasching, Peter A
AU - Figueroa, Jonine
AU - Flyger, Henrik
AU - Fostira, Florentia
AU - García-Closas, Montserrat
AU - Giles, Graham G
AU - Australian Ovarian Cancer Study Group
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
PY - 2016/5
Y1 - 2016/5
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1136/jmedgenet-2015-103529
DO - 10.1136/jmedgenet-2015-103529
M3 - Journal article
C2 - 26921362
VL - 53
SP - 298
EP - 309
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
ER -
ID: 171996457