TY - JOUR
T1 - No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk
T2 - Implications for gene panel testing
AU - Australian Ovarian Cancer Study Group
AU - kConFab Investigators
AU - Lifepool Investigators
AU - NBCS Investigators
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 - Torres, Diana
N1 - Funding Information:
The ABCS study was supported by the Dutch Cancer Society (grants NKI 2007-3839; 2009 4363). The ACP study is funded by the Breast Cancer Research Trust, UK. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer (recently merged with Breast Cancer Campaign forming Breast Cancer Now) and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). (BIGGS) ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, UK. IT is supported by the Oxford Biomedical Research Centre. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398). Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR). The MEC was support by NIH grants CA63464, CA54281, CA098758 and CA132839. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR), London.
PY - 2016/2/26
Y1 - 2016/2/26
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.
UR - https://www.scopus.com/pages/publications/84959299225
U2 - 10.1136/jmedgenet-2015-103529
DO - 10.1136/jmedgenet-2015-103529
M3 - Article
C2 - 26921362
AN - SCOPUS:84959299225
SN - 0022-2593
VL - 53
SP - 298
EP - 309
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 5
ER -
SDG 3 Good Health and Well-being