Citation
Levi, Hagai; Carmi, Shai; Rosset, Saharon; Yerushalmi, Rinat; Zick, Aviad; Yablonski-Peretz, Tamar; Wang, Qin; Bolla, Manjeet K.; Dennis, Joe; & Michailidou, Kyriaki, et al. (2023). Evaluation of European-Based Polygenic Risk Score for Breast Cancer in Ashkenazi Jewish Women in Israel. Journal of Medical Genetics, 60(12), 1186-1197.Abstract
BACKGROUND: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.METHODS: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.
RESULTS: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).
CONCLUSIONS: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.
URL
http://dx.doi.org/10.1136/jmg-2023-109185Reference Type
Journal ArticleYear Published
2023Journal Title
Journal of Medical GeneticsAuthor(s)
Levi, HagaiCarmi, Shai
Rosset, Saharon
Yerushalmi, Rinat
Zick, Aviad
Yablonski-Peretz, Tamar
Wang, Qin
Bolla, Manjeet K.
Dennis, Joe
Michailidou, Kyriaki
Lush, Michael
Ahearn, Thomas U.
Andrulis, Irene L.
Anton-Culver, Hoda
Antoniou, Antonis C.
Arndt, Volker
Augustinsson, Annelie
Auvinen, Päivi K.
Beane Freeman, Laura E.
Beckmann, Matthias W.
Behrens, Sabine
Bermisheva, Marina
Bodelon, Clara
Bogdanova, Natalia V.
Bojesen, Stig E.
Brenner, Hermann
Byers, Helen
Camp, Nicola J.
Castelao, Jose E.
Chang-Claude, Jenny
Chirlaque, María-Dolores
Chung, Wendy K.
Clarke, Christine L.
Collee, Margriet J.
Colonna, Sarah V.
Couch, Fergus J.
Cox, Angela
Cross, Simon S.
Czene, Kamila
Daly, Mary B.
Devilee, Peter
Dork, Thilo
Dossus, Laure
Eccles, Diana M.
Eliassen, A. Heather
Eriksson, Mikael
Evans, Gareth D.
Fasching, Peter A.
Fletcher, Olivia
Flyger, Henrik
Fritschi, Lin
Gabrielson, Marike
Gago-Dominguez, Manuela
García-Closas, Montserrat
Garcia-Saenz, Jose A.
Genkinger, Jeanine
Giles, Graham G.
Goldberg, Mark S.
Guénel, Pascal
Hall, Per
Hamann, Ute
He, Wei
Hillemanns, Peter
Hollestelle, Antoinette
Hoppe, Reiner
Hopper, John L.
ABCTB Investigators
Jakovchevska, Simona
Jakubowska, Anna
Jernström, Helena
John, Esther M.
Johnson, Nichola
Jones, Michael E.
Vijai, Joseph
Kaaks, Rudolf
Khusnutdinova, Elza
Kitahara, Cari M.
Koutros, Stella
Kristensen, Vessela N.
Kurian, Allison W.
Lacey, James V.
Lambrechts, Diether
Le Marchand, Loic
Lejbkowicz, Flavio
Lindblom, Annika
Loibl, Sibylle
Lori, Adriana
Lubinski, Jan
Mannermaa, Arto
Manoochehri, Mehdi
Mavroudis, Dimitrios
Menon, Usha
Mulligan, Anna Marie
Murphy, Rachel A.
Nevelsteen, Ines
Newman, William G.
Obi, Nadia
O'Brien, Katie M.
Offit, Ken
Olshan, Andrew F.
Plaseska-Karanfilska, Dijana
Olson, Janet E.
Panico, Salvatore
Park-Simon, Tjoung-Won
Patel, Alpa V.
Peterlongo, Paolo
Rack, Brigitte
Radice, Paolo
Rennert, Gad
Rhenius, Valerie
Romero, Atocha
Saloustros, Emmanouil
Sandler, Dale P.
Schmidt, Marjanka K.
Schwentner, Lukas
Shah, Mitul
Sharma, Priyanka
Simard, Jacques
Southey, Melissa C.
Stone, Jennifer
Tapper, William J.
Taylor, Jack A.
Teras, Lauren R.
Toland, Amanda E.
Troester, Melissa A.
Truong, Thérèse
van der Kolk, Lizet E.
Weinberg, Clarice R.
Wendt, Camilla
Yang, Xiaohong R.
Zheng, Wei
Ziogas, Argyrios
Dunning, Alison M.
Pharoah, Paul
Easton, Douglas F.
Ben-Sachar, Shay
Elefant, Naama
Shamir, Ron
Elkon, Ran