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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- Source :
- Hakkaart, C, Pearson, J F, Marquart, L, Dennis, J, Wiggins, G A R, Barnes, D R, Robinson, B A, Mace, P D, Aittomäki, K, Andrulis, I L, Arun, B K, Azzollini, J, Balmaña, J, Barkardottir, R B, Belhadj, S, Berger, L, Blok, M J, Boonen, S E, Borde, J, Bradbury, A R, Brunet, J, Buys, S S, Caligo, M A, Campbell, I, Chung, W K, Claes, K B M, GEMO Study Collaborators, EMBRACE Collaborators, Collonge-Rame, M A, Cook, J, Cosgrove, C, Couch, F J, Daly, M B, Dandiker, S, Davidson, R, de la Hoya, M, de Putter, R, Delnatte, C, Dhawan, M, Diez, O, Ding, Y C, Domchek, S M, Donaldson, A, Eason, J, Easton, D F, Ehrencrona, H, Engel, C, Evans, D G, Faust, U, Hansen, T V O, SWE-BRCA Investigators, KConFab Investigators, HEBON Investigators, Lautrup, C & Pedersen, I S 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, 1061 . https://doi.org/10.1038/s42003-022-03978-6, Hakkaart, C, Pearson, J F, Marquart, L, Dennis, J, Wiggins, G A R, Barnes, D R, Robinson, B A, Mace, P D, Aittomäki, K, Andrulis, I L, Arun, B K, Azzollini, J, Balmaña, J, Barkardottir, R B, Belhadj, S, Berger, L, Blok, M J, Boonen, S E, Borde, J, Bradbury, A R, Brunet, J, Buys, S S, Caligo, M A, Campbell, I, Chung, W K, Claes, K B M, Collonge-Rame, M-A, Cook, J, Cosgrove, C, Couch, F J, Daly, M B, Dandiker, S, Davidson, R, de la Hoya, M, de Putter, R, Delnatte, C, Dhawan, M, Diez, O, Ding, Y C, Domchek, S M, Donaldson, A, Eason, J, Easton, D F, Ehrencrona, H, Engel, C, Evans, D G, Faust, U, Feliubadaló, L, Fostira, F, Friedman, E, Frone, M, Frost, D, Garber, J, Gayther, S A, Gehrig, A, Gesta, P, Godwin, A K, Goldgar, D E, Greene, M H, Hahnen, E, Hake, C R, Hamann, U, Hansen, T V O, Hauke, J, Hentschel, J, Herold, N, Honisch, E, Hulick, P J, Imyanitov, E N, Isaacs, C, Izatt, L, Izquierdo, A, Jakubowska, A, James, P A, Janavicius, R, John, E M, Joseph, V, Karlan, B Y, Kemp, Z, Kirk, J, Konstantopoulou, I, Koudijs, M, Kwong, A, Laitman, Y, Lalloo, F, Lasset, C, Lautrup, C, Lazaro, C, Legrand, C, Leslie, G, Lesueur, F, Mai, P L, Manoukian, S, Mari, V, Martens, J W M, McGuffog, L, Mebirouk, N, Meindl, A, Miller, A, Montagna, M, Moserle, L, Mouret-Fourme, E, Musgrave, H, Nambot, S, Nathanson, K L, Neuhausen, S L, Nevanlinna, H, Yie, J N Y, Nguyen-Dumont, T, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, O I, Osorio, A, Ott, C-E, Park, S K, Parsons, M T, Pedersen, I S, Peixoto, A, Perez-Segura, P, Peterlongo, P, Pocza, T, Radice, P, Ramser, J, Rantala, J, Rodriguez, G C, Rønlund, K, Rosenberg, E H, Rossing, M, Schmutzler, R K, Shah, P D, Sharif, S, Sharma, P, Side, L E, Simard, J, Singer, C F, Snape, K, Steinemann, D, Stoppa-Lyonnet, D, Sutter, C, Tan, Y Y, Teixeira, M R, Teo, S H, Thomassen, M, Thull, D L, Tischkowitz, M, Toland, A E, Trainer, A H, Tripathi, V, Tung, N, van Engelen, K, van Rensburg, E J, Vega, A, Viel, A, Walker, L, Weitzel, J N, Wevers, M R, Chenevix-Trench, G, Spurdle, A B, Antoniou, A C, Walker, L C & GEMO Study Collaborators 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, no. 1, 1061, pp. 1061 . https://doi.org/10.1038/s42003-022-03978-6, Communications Biology, 5(1):1061. Nature Publishing Group, Hakkaart, C, Pearson, J F, Marquart, L, Dennis, J, Wiggins, G A R, Barnes, D R, Robinson, B A, Mace, P D, Aittomäki, K, Andrulis, I L, Arun, B K, Azzollini, J, Balmaña, J, Barkardottir, R B, Belhadj, S, Berger, L, Blok, M J, Boonen, S E, Borde, J, Bradbury, A R, Brunet, J, Buys, S S, Caligo, M A, Campbell, I, Chung, W K, Claes, K B M, Collonge-Rame, M-A, Cook, J, Cosgrove, C, Couch, F J, Daly, M B, Dandiker, S, Davidson, R, de la Hoya, M, de Putter, R, Delnatte, C, Dhawan, M, Diez, O, Ding, Y C, Domchek, S M, Donaldson, A, Eason, J, Easton, D F, Ehrencrona, H, Engel, C, Evans, D G, Faust, U, Feliubadaló, L, Fostira, F, Hansen, T V O, Rossing, C M, GEMO Study Collaborators, EMBRACE Collaborators, SWE-BRCA Investigators, kConFab Investigators & HEBON Investigators 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, 1061 . https://doi.org/10.1038/s42003-022-03978-6, COMMUNICATIONS BIOLOGY, Scientia, GEMO Study Collaborators, EMBRACE Collaborators, SWE-BRCA Investigators, KConFab Investigators & HEBON Investigators 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, no. 1, pp. 1061 . https://doi.org/10.1038/s42003-022-03978-6, Communications biology, Berlin : Nature Portfolio, 2022, vol. 5, no. 1, art. no. 1061, p. [1-15], Communications Biology, 5(1). Springer Nature, Communications biology, 5:1061. Nature Publishing Group
- Publication Year :
- 2022
-
Abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
- Subjects :
- Estrogen-metabolizing enzymes
Heterozygote
DNA Copy Number Variations
Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES]
Messenger
Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES]
Medicine (miscellaneous)
Expression
Genetics and Molecular Biology
Breast Neoplasms
Breast Neoplasms/genetics
Genetic polymorphisms
Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Genomic Structural Variation::DNA Copy Number Variations [PHENOMENA AND PROCESSES]
General Biochemistry, Genetics and Molecular Biology
Dna-adducts
Association
Mama - Càncer - Propensió
SDG 3 - Good Health and Well-being
Other subheadings::Other subheadings::/genetics [Other subheadings]
Medicine and Health Sciences
Humans
Genetic Predisposition to Disease
Familial breast
RNA, Messenger
fenómenos genéticos::variación genética::polimorfismo genético::variación estructural genómica::variaciones del número de copias de ADN [FENÓMENOS Y PROCESOS]
fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS]
BRCA2 Protein
neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES]
Otros calificadores::Otros calificadores::/genética [Otros calificadores]
BRCA1 Protein
Isoform 1a1 sult1a1
Sulfotransferase
BRCA2 Protein/genetics
Genòmica
Ovarian
General Biochemistry
Mama - Càncer - Aspectes genètics
RNA
BRCA1 Protein/genetics
Female
3111 Biomedicine
General Agricultural and Biological Sciences
Brca1
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Database :
- OpenAIRE
- Journal :
- Hakkaart, C, Pearson, J F, Marquart, L, Dennis, J, Wiggins, G A R, Barnes, D R, Robinson, B A, Mace, P D, Aittomäki, K, Andrulis, I L, Arun, B K, Azzollini, J, Balmaña, J, Barkardottir, R B, Belhadj, S, Berger, L, Blok, M J, Boonen, S E, Borde, J, Bradbury, A R, Brunet, J, Buys, S S, Caligo, M A, Campbell, I, Chung, W K, Claes, K B M, GEMO Study Collaborators, EMBRACE Collaborators, Collonge-Rame, M A, Cook, J, Cosgrove, C, Couch, F J, Daly, M B, Dandiker, S, Davidson, R, de la Hoya, M, de Putter, R, Delnatte, C, Dhawan, M, Diez, O, Ding, Y C, Domchek, S M, Donaldson, A, Eason, J, Easton, D F, Ehrencrona, H, Engel, C, Evans, D G, Faust, U, Hansen, T V O, SWE-BRCA Investigators, KConFab Investigators, HEBON Investigators, Lautrup, C & Pedersen, I S 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, 1061 . https://doi.org/10.1038/s42003-022-03978-6, Hakkaart, C, Pearson, J F, Marquart, L, Dennis, J, Wiggins, G A R, Barnes, D R, Robinson, B A, Mace, P D, Aittomäki, K, Andrulis, I L, Arun, B K, Azzollini, J, Balmaña, J, Barkardottir, R B, Belhadj, S, Berger, L, Blok, M J, Boonen, S E, Borde, J, Bradbury, A R, Brunet, J, Buys, S S, Caligo, M A, Campbell, I, Chung, W K, Claes, K B M, Collonge-Rame, M-A, Cook, J, Cosgrove, C, Couch, F J, Daly, M B, Dandiker, S, Davidson, R, de la Hoya, M, de Putter, R, Delnatte, C, Dhawan, M, Diez, O, Ding, Y C, Domchek, S M, Donaldson, A, Eason, J, Easton, D F, Ehrencrona, H, Engel, C, Evans, D G, Faust, U, Feliubadaló, L, Fostira, F, Friedman, E, Frone, M, Frost, D, Garber, J, Gayther, S A, Gehrig, A, Gesta, P, Godwin, A K, Goldgar, D E, Greene, M H, Hahnen, E, Hake, C R, Hamann, U, Hansen, T V O, Hauke, J, Hentschel, J, Herold, N, Honisch, E, Hulick, P J, Imyanitov, E N, Isaacs, C, Izatt, L, Izquierdo, A, Jakubowska, A, James, P A, Janavicius, R, John, E M, Joseph, V, Karlan, B Y, Kemp, Z, Kirk, J, Konstantopoulou, I, Koudijs, M, Kwong, A, Laitman, Y, Lalloo, F, Lasset, C, Lautrup, C, Lazaro, C, Legrand, C, Leslie, G, Lesueur, F, Mai, P L, Manoukian, S, Mari, V, Martens, J W M, McGuffog, L, Mebirouk, N, Meindl, A, Miller, A, Montagna, M, Moserle, L, Mouret-Fourme, E, Musgrave, H, Nambot, S, Nathanson, K L, Neuhausen, S L, Nevanlinna, H, Yie, J N Y, Nguyen-Dumont, T, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, O I, Osorio, A, Ott, C-E, Park, S K, Parsons, M T, Pedersen, I S, Peixoto, A, Perez-Segura, P, Peterlongo, P, Pocza, T, Radice, P, Ramser, J, Rantala, J, Rodriguez, G C, Rønlund, K, Rosenberg, E H, Rossing, M, Schmutzler, R K, Shah, P D, Sharif, S, Sharma, P, Side, L E, Simard, J, Singer, C F, Snape, K, Steinemann, D, Stoppa-Lyonnet, D, Sutter, C, Tan, Y Y, Teixeira, M R, Teo, S H, Thomassen, M, Thull, D L, Tischkowitz, M, Toland, A E, Trainer, A H, Tripathi, V, Tung, N, van Engelen, K, van Rensburg, E J, Vega, A, Viel, A, Walker, L, Weitzel, J N, Wevers, M R, Chenevix-Trench, G, Spurdle, A B, Antoniou, A C, Walker, L C & GEMO Study Collaborators 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, no. 1, 1061, pp. 1061 . https://doi.org/10.1038/s42003-022-03978-6, Communications Biology, 5(1):1061. Nature Publishing Group, Hakkaart, C, Pearson, J F, Marquart, L, Dennis, J, Wiggins, G A R, Barnes, D R, Robinson, B A, Mace, P D, Aittomäki, K, Andrulis, I L, Arun, B K, Azzollini, J, Balmaña, J, Barkardottir, R B, Belhadj, S, Berger, L, Blok, M J, Boonen, S E, Borde, J, Bradbury, A R, Brunet, J, Buys, S S, Caligo, M A, Campbell, I, Chung, W K, Claes, K B M, Collonge-Rame, M-A, Cook, J, Cosgrove, C, Couch, F J, Daly, M B, Dandiker, S, Davidson, R, de la Hoya, M, de Putter, R, Delnatte, C, Dhawan, M, Diez, O, Ding, Y C, Domchek, S M, Donaldson, A, Eason, J, Easton, D F, Ehrencrona, H, Engel, C, Evans, D G, Faust, U, Feliubadaló, L, Fostira, F, Hansen, T V O, Rossing, C M, GEMO Study Collaborators, EMBRACE Collaborators, SWE-BRCA Investigators, kConFab Investigators & HEBON Investigators 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, 1061 . https://doi.org/10.1038/s42003-022-03978-6, COMMUNICATIONS BIOLOGY, Scientia, GEMO Study Collaborators, EMBRACE Collaborators, SWE-BRCA Investigators, KConFab Investigators & HEBON Investigators 2022, ' Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers ', Communications Biology, vol. 5, no. 1, pp. 1061 . https://doi.org/10.1038/s42003-022-03978-6, Communications biology, Berlin : Nature Portfolio, 2022, vol. 5, no. 1, art. no. 1061, p. [1-15], Communications Biology, 5(1). Springer Nature, Communications biology, 5:1061. Nature Publishing Group
- Accession number :
- edsair.doi.dedup.....63f076631390a033b9bcb1c10313c400