Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
Creators: name: Barnes, Daniel R.
name: Rookus, Matti A.
name: McGuffog, Lesley
name: Leslie, Goska
name: Mooij, Thea M.
name: Dennis, Joe
name: Mavaddat, Nasim
name: Adlard, Julian
name: Ahmed, Munaza
name: Aittomäki, Kristiina
name: Andrieu, Nadine
name: Andrulis, Irene L.
name: Arnold, Norbert
name: Arun, Banu K.
name: Azzollini, Jacopo
name: Balmaña, Judith
name: Barkardottir, Rosa B.
name: Barrowdale, Daniel
name: Benitez, Javier
name: Berthet, Pascaline
name: Białkowska, Katarzyna
name: Blanco, Amie M.
name: Blok, Marinus J.
name: Bonanni, Bernardo
name: Boonen, Susanne E.
name: Borg, Åke
name: Bozsik, Aniko
name: Bradbury, Angela R.
name: Brennan, Paul
name: Brewer, Carole
name: Brunet, Joan
name: Buys, Saundra S.
name: Caldés, Trinidad
name: Caligo, Maria A.
name: Campbell, Ian
name: Christensen, Lise Lotte
name: Chung, Wendy K.
name: Claes, Kathleen B. M.
name: Colas, Chrystelle
name: Collonge-Rame, Marie-Agnès
name: Cook, Jackie
name: Daly, Mary B.
name: Davidson, Rosemarie
name: De La Hoya, Miguel
name: De Putter, Robin
name: Delnatte, Capucine
name: Devilee, Peter
name: Diez, Orland
name: Ding, Yuan Chun
name: Domchek, Susan M.
name: Dorfling, Cecilia M.
name: Dumont, Martine
name: Eeles, Ros
name: Ejlertsen, Bent
name: Engel, Christoph
name: Evans, D. Gareth
name: Faivre, Laurence
name: Foretova, Lenka
name: Fostira, Florentia
name: Friedlander, Michael
name: Friedman, Eitan
name: Frost, Debra
name: Ganz, Patricia A.
name: Garber, Judy
name: Gehrig, Andrea
name: Gerdes, Anne-Marie
name: Gesta, Paul
name: Giraud, Sophie
name: Glendon, Gord
name: Godwin, Andrew K.
name: Goldgar, David E.
name: González-Neira, Anna
name: Greene, Mark H.
name: Gschwantler-Kaulich, Daphne
name: Hahnen, Eric
name: Hamann, Ute
name: Hanson, Helen
name: Hentschel, Julia
name: Hogervorst, Frans B. L.
name: Hooning, Maartje J.
name: Horvath, Judit
name: Hu, Chunling
name: Hulick, Peter J.
name: Imyanitov, Evgeny N.
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: Kast, Karin
name: Koudijs, Marco
name: Kruse, Torben A.
name: Kwong, Ava
name: Laitman, Yael
name: Lasset, Christine
name: Lazaro, Conxi
name: Lester, Jenny
name: Lesueur, Fabienne
name: Liljegren, Annelie
name: Loud, Jennifer T.
name: Lubiński, Jan
name: Mai, Phuong L.
name: Manoukian, Siranoush
name: Mari, Véronique
name: Mebirouk, Noura
name: Meijers-Heijboer, Hanne E. J.
name: Meindl, Alfons
name: Mensenkamp, Arjen R.
name: Miller, Austin
name: Montagna, Marco
name: Mouret-Fourme, Emmanuelle
name: Mukherjee, Semanti
name: Mulligan, Anna Marie
name: Nathanson, Katherine L.
name: Neuhausen, Susan L.
name: Nevanlinna, Heli
name: Niederacher, Dieter
name: Nielsen, Finn Cilius
name: Nikitina-Zake, Liene
name: Noguès, Catherine
name: Olah, Edith
name: Olopade, Olufunmilayo I.
name: Ong, Kai-Ren
name: O’Shaughnessy-Kirwan, Aoife
name: Osorio, Ana
name: Ott, Claus-Eric
name: Papi, Laura
name: Park, Sue K.
name: Parsons, Michael T.
name: Pedersen, Inge Sokilde
name: Peissel, Bernard
name: Peixoto, Ana
name: Peterlongo, Paolo
name: Pfeiler, Georg
name: Phillips, Kelly-Anne
name: Prajzendanc, Karolina
name: Pujana, Miquel Angel
name: Radice, Paolo
name: Ramser, Juliane
name: Ramus, Susan J.
name: Rantala, Johanna
name: Rennert, Gad
name: Risch, Harvey A.
name: Robson, Mark
name: Rønlund, Karina
name: Salani, Ritu
name: Schuster, Hélène
name: Senter, Leigha
name: Shah, Payal D.
name: Sharma, Priyanka
name: Side, Lucy E.
name: Singer, Christian F.
name: Slavin, Thomas P.
name: Soucy, Penny
name: Southey, Melissa C.
name: Spurdle, Amanda B.
name: Steinemann, Doris
name: Steinsnyder, Zoe
name: Stoppa-Lyonnet, Dominique
name: Sutter, Christian
name: Tan, Yen Yen
name: Teixeira, Manuel R.
name: Teo, Soo Hwang
name: Thull, Darcy L.
name: Tischkowitz, Marc
name: Tognazzo, Silvia
name: Toland, Amanda E.
name: Trainer, Alison H.
name: Tung, Nadine
name: Van Engelen, Klaartje
name: Van Rensburg, Elizabeth J.
name: Vega, Ana
name: Vierstraete, Jeroen
name: Wagner, Gabriel
name: Walker, Lisa
name: Wang-Gohrke, Shan
name: Wappenschmidt, Barbara
name: Weitzel, Jeffrey N.
name: Yadav, Siddhartha
name: Yang, Xin
name: Yannoukakos, Drakoulis
name: Zimbalatti, Dario
name: Offit, Kenneth
name: Thomassen, Mads
name: Couch, Fergus J.
name: Schmutzler, Rita K.
name: Simard, Jacques
name: Easton, Douglas F.
name: Chenevix-Trench, Georgia
name: Antoniou, Antonis C.
name: Antoniou, Antonis
name: Easton, Douglas
name: Side, Lucy
name: Spurdle, Amanda
name: Blok, Marinus
name: Hogervorst, Frans
name: Hooning, Maartje
name: Mensenkamp, Arjen
name: Meijers-Heijboer, Hanne
name: Rookus, Matti
name: Engelen, Klaartje Van
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Article
article
BRCA1/2
breast cancer
ovarian cancer
PRS
genetics

description: Abstract: 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: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25–1.33], P = 3×10−72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27–1.36], P = 7×10−50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25–1.40], P = 3×10−22) and BRCA2 (HR = 1.44 [95% CI 1.30–1.60], P = 4×10−12) carriers. The associations in the prospective cohort were similar. Conclusion: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.