Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.
Creators: name: Hakkaart, Christopher
name: Pearson, John F
name: Marquart, Louise
name: Dennis, Joe
name: Wiggins, George AR
name: Barnes, Daniel R
name: Robinson, Bridget A
name: Mace, Peter D
name: Aittomäki, Kristiina
name: Andrulis, Irene L
name: Arun, Banu K
name: Azzollini, Jacopo
name: Balmaña, Judith
name: Barkardottir, Rosa B
name: Belhadj, Sami
name: Berger, Lieke
name: Blok, Marinus J
name: Boonen, Susanne E
name: Borde, Julika
name: Bradbury, Angela R
name: Brunet, Joan
name: Buys, Saundra S
name: Caligo, Maria A
name: Campbell, Ian
name: Chung, Wendy K
name: Claes, Kathleen BM
name: GEMO Study Collaborators
name: EMBRACE Collaborators
name: Collonge-Rame, Marie-Agnès
name: Cook, Jackie
name: Cosgrove, Casey
name: Couch, Fergus J
name: Daly, Mary B
name: Dandiker, Sita
name: Davidson, Rosemarie
name: De La Hoya, Miguel
name: De Putter, Robin
name: Delnatte, Capucine
name: Dhawan, Mallika
name: Diez, Orland
name: Ding, Yuan Chun
name: Domchek, Susan M
name: Donaldson, Alan
name: Eason, Jacqueline
name: Easton, Douglas F
name: Ehrencrona, Hans
name: Engel, Christoph
name: Evans, D Gareth
name: Faust, Ulrike
name: Feliubadaló, Lidia
name: Fostira, Florentia
name: Friedman, Eitan
name: Frone, Megan
name: Frost, Debra
name: Garber, Judy
name: Gayther, Simon A
name: Gehrig, Andrea
name: Gesta, Paul
name: Godwin, Andrew K
name: Goldgar, David E
name: Greene, Mark H
name: Hahnen, Eric
name: Hake, Christopher R
name: Hamann, Ute
name: Hansen, Thomas VO
name: Hauke, Jan
name: Hentschel, Julia
name: Herold, Natalie
name: Honisch, Ellen
name: Hulick, Peter J
name: Imyanitov, Evgeny N
name: SWE-BRCA Investigators
name: KConFab Investigators
name: HEBON Investigators
name: Isaacs, Claudine
name: Izatt, Louise
name: Izquierdo, Angel
name: Jakubowska, Anna
name: James, Paul A
name: Janavicius, Ramunas
name: John, Esther M
name: Joseph, Vijai
name: Karlan, Beth Y
name: Kemp, Zoe
name: Kirk, Judy
name: Konstantopoulou, Irene
name: Koudijs, Marco
name: Kwong, Ava
name: Laitman, Yael
name: Lalloo, Fiona
name: Lasset, Christine
name: Lautrup, Charlotte
name: Lazaro, Conxi
name: Legrand, Clémentine
name: Leslie, Goska
name: Lesueur, Fabienne
name: Mai, Phuong L
name: Manoukian, Siranoush
name: Mari, Véronique
name: Martens, John WM
name: McGuffog, Lesley
name: Mebirouk, Noura
name: Meindl, Alfons
name: Miller, Austin
name: Montagna, Marco
name: Moserle, Lidia
name: Mouret-Fourme, Emmanuelle
name: Musgrave, Hannah
name: Nambot, Sophie
name: Nathanson, Katherine L
name: Neuhausen, Susan L
name: Nevanlinna, Heli
name: Yie, Joanne Ngeow Yuen
name: Nguyen-Dumont, Tu
name: Nikitina-Zake, Liene
name: Offit, Kenneth
name: Olah, Edith
name: Olopade, Olufunmilayo I
name: Osorio, Ana
name: Ott, Claus-Eric
name: Park, Sue K
name: Parsons, Michael T
name: Pedersen, Inge Sokilde
name: Peixoto, Ana
name: Perez-Segura, Pedro
name: Peterlongo, Paolo
name: Pocza, Timea
name: Radice, Paolo
name: Ramser, Juliane
name: Rantala, Johanna
name: Rodriguez, Gustavo C
name: Rønlund, Karina
name: Rosenberg, Efraim H
name: Rossing, Maria
name: Schmutzler, Rita K
name: Shah, Payal D
name: Sharif, Saba
name: Sharma, Priyanka
name: Side, Lucy E
name: Simard, Jacques
name: Singer, Christian F
name: Snape, Katie
name: Steinemann, Doris
name: Stoppa-Lyonnet, Dominique
name: Sutter, Christian
name: Tan, Yen Yen
name: Teixeira, Manuel R
name: Teo, Soo Hwang
name: Thomassen, Mads
name: Thull, Darcy L
name: Tischkowitz, Marc
name: Toland, Amanda E
name: Trainer, Alison H
name: Tripathi, Vishakha
name: Tung, Nadine
name: Van Engelen, Klaartje
name: Van Rensburg, Elizabeth J
name: Vega, Ana
name: Viel, Alessandra
name: Walker, Lisa
name: Weitzel, Jeffrey N
name: Wevers, Marike R
name: Chenevix-Trench, Georgia
name: Spurdle, Amanda B
name: Antoniou, Antonis C
name: Walker, Logan C
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Article
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/692/4028/67
/45/43
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/45/77
/45/90
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article

description: 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.
description: C12292/A20861 PPRPGM-Nov20\100002