Skip to main content
Download PDF
- Main
Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
- Barnes, Daniel R;
- Rookus, Matti A;
- McGuffog, Lesley;
- Leslie, Goska;
- Mooij, Thea M;
- Dennis, Joe;
- Mavaddat, Nasim;
- Adlard, Julian;
- Ahmed, Munaza;
- Aittomäki, Kristiina;
- Andrieu, Nadine;
- Andrulis, Irene L;
- Arnold, Norbert;
- Arun, Banu K;
- Azzollini, Jacopo;
- Balmaña, Judith;
- Barkardottir, Rosa B;
- Barrowdale, Daniel;
- Benitez, Javier;
- Berthet, Pascaline;
- Białkowska, Katarzyna;
- Blanco, Amie M;
- Blok, Marinus J;
- Bonanni, Bernardo;
- Boonen, Susanne E;
- Borg, Åke;
- Bozsik, Aniko;
- Bradbury, Angela R;
- Brennan, Paul;
- Brewer, Carole;
- Brunet, Joan;
- Buys, Saundra S;
- Caldés, Trinidad;
- Caligo, Maria A;
- Campbell, Ian;
- Christensen, Lise Lotte;
- Chung, Wendy K;
- Claes, Kathleen BM;
- Colas, Chrystelle;
- Collonge-Rame, Marie-Agnès;
- Cook, Jackie;
- Daly, Mary B;
- Davidson, Rosemarie;
- de la Hoya, Miguel;
- de Putter, Robin;
- Delnatte, Capucine;
- Devilee, Peter;
- Diez, Orland;
- Ding, Yuan Chun;
- Domchek, Susan M;
- Dorfling, Cecilia M;
- Dumont, Martine;
- Eeles, Ros;
- Ejlertsen, Bent;
- Engel, Christoph;
- Evans, D Gareth;
- Faivre, Laurence;
- Foretova, Lenka;
- Fostira, Florentia;
- Friedlander, Michael;
- Friedman, Eitan;
- Frost, Debra;
- Ganz, Patricia A;
- Garber, Judy;
- Gehrig, Andrea;
- Gerdes, Anne-Marie;
- Gesta, Paul;
- Giraud, Sophie;
- Glendon, Gord;
- Godwin, Andrew K;
- Goldgar, David E;
- González-Neira, Anna;
- Greene, Mark H;
- Gschwantler-Kaulich, Daphne;
- Hahnen, Eric;
- Hamann, Ute;
- Hanson, Helen;
- Hentschel, Julia;
- Hogervorst, Frans BL;
- Hooning, Maartje J;
- Horvath, Judit;
- Hu, Chunling;
- Hulick, Peter J;
- Imyanitov, Evgeny N;
- Isaacs, Claudine;
- Izatt, Louise;
- Izquierdo, Angel;
- Jakubowska, Anna;
- James, Paul A;
- Janavicius, Ramunas;
- John, Esther M;
- Joseph, Vijai;
- Karlan, Beth Y;
- Kast, Karin;
- Koudijs, Marco;
- Kruse, Torben A;
- Kwong, Ava;
- Laitman, Yael;
- Lasset, Christine;
- Lazaro, Conxi;
- Lester, Jenny;
- Lesueur, Fabienne;
- Liljegren, Annelie;
- Loud, Jennifer T;
- Lubiński, Jan;
- Mai, Phuong L;
- Manoukian, Siranoush;
- Mari, Véronique;
- Mebirouk, Noura;
- Meijers-Heijboer, Hanne EJ;
- Meindl, Alfons;
- Mensenkamp, Arjen R;
- Miller, Austin;
- Montagna, Marco;
- Mouret-Fourme, Emmanuelle;
- Mukherjee, Semanti;
- Mulligan, Anna Marie;
- Nathanson, Katherine L;
- Neuhausen, Susan L;
- Nevanlinna, Heli;
- Niederacher, Dieter;
- Nielsen, Finn Cilius;
- Nikitina-Zake, Liene;
- Noguès, Catherine;
- Olah, Edith;
- Olopade, Olufunmilayo I;
- Ong, Kai-ren;
- O’Shaughnessy-Kirwan, Aoife;
- Osorio, Ana;
- Ott, Claus-Eric;
- Papi, Laura;
- Park, Sue K;
- Parsons, Michael T;
- Pedersen, Inge Sokilde;
- Peissel, Bernard;
- Peixoto, Ana;
- Peterlongo, Paolo;
- Pfeiler, Georg;
- Phillips, Kelly-Anne;
- Prajzendanc, Karolina;
- Pujana, Miquel Angel;
- Radice, Paolo;
- Ramser, Juliane;
- Ramus, Susan J;
- Rantala, Johanna;
- Rennert, Gad;
- Risch, Harvey A;
- Robson, Mark;
- Rønlund, Karina;
- Salani, Ritu;
- Schuster, Hélène;
- Senter, Leigha;
- Shah, Payal D;
- Sharma, Priyanka;
- Side, Lucy E;
- Singer, Christian F;
- Slavin, Thomas P;
- Soucy, Penny;
- Southey, Melissa C;
- Spurdle, Amanda B;
- Steinemann, Doris;
- Steinsnyder, Zoe;
- Stoppa-Lyonnet, Dominique;
- Sutter, Christian;
- Tan, Yen Yen;
- Teixeira, Manuel R;
- Teo, Soo Hwang;
- Thull, Darcy L;
- Tischkowitz, Marc;
- Tognazzo, Silvia;
- Toland, Amanda E;
- Trainer, Alison H;
- Tung, Nadine;
- van Engelen, Klaartje;
- van Rensburg, Elizabeth J;
- Vega, Ana;
- Vierstraete, Jeroen;
- Wagner, Gabriel;
- Walker, Lisa;
- Wang-Gohrke, Shan;
- Wappenschmidt, Barbara;
- Weitzel, Jeffrey N;
- Yadav, Siddhartha;
- Yang, Xin;
- Yannoukakos, Drakoulis;
- Zimbalatti, Dario;
- Offit, Kenneth;
- Thomassen, Mads;
- Couch, Fergus J;
- Schmutzler, Rita K;
- Simard, Jacques;
- Easton, Douglas F;
- Chenevix-Trench, Georgia;
- Antoniou, Antonis C
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
For improved accessibility of PDF content, download the file to your device.
Enter the password to open this PDF file:
File name:
-
File size:
-
Title:
-
Author:
-
Subject:
-
Keywords:
-
Creation Date:
-
Modification Date:
-
Creator:
-
PDF Producer:
-
PDF Version:
-
Page Count:
-
Page Size:
-
Fast Web View:
-
Preparing document for printing…
0%