Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel.
Hagai Levi,
Shai Carmi,
Saharon Rosset,
Rinat Yerushalmi,
Aviad Zick,
Tamar Yablonski-Peretz,
,
Qin Wang,
Manjeet K Bolla,
Joe Dennis,
Kyriaki Michailidou,
Michael Lush,
Thomas Ahearn,
Irene L Andrulis,
Hoda Anton-Culver,
Antonis C Antoniou,
Volker Arndt,
Annelie Augustinsson,
Päivi Auvinen,
Laura Beane Freeman,
Matthias Beckmann,
Sabine Behrens,
Marina Bermisheva,
Clara Bodelon,
Natalia V Bogdanova,
Stig E Bojesen,
Hermann Brenner,
Helen Byers,
Nicola Camp,
Jose Castelao,
Jenny Chang-Claude,
María-Dolores Chirlaque,
Wendy Chung,
Christine Clarke,
,
Margriet J Collee,
Sarah Colonna,
,
Fergus Couch,
Angela Cox,
Simon S Cross,
Kamila Czene,
Mary Daly,
Peter Devilee,
Thilo Dork,
Laure Dossus,
Diana M Eccles,
A Heather Eliassen,
Mikael Eriksson,
Gareth Evans,
Peter Fasching,
Olivia Fletcher,
Henrik Flyger,
Lin Fritschi,
Marike Gabrielson,
Manuela Gago-Dominguez,
Montserrat García-Closas,
Jose Angel Garcia-Saenz,
Jeanine Genkinger,
Graham G Giles,
Mark Goldberg,
Pascal Guénel,
Per Hall,
Ute Hamann,
Wei He,
Peter Hillemanns,
Antoinette Hollestelle,
Reiner Hoppe,
John Hopper,
,
Simona Jakovchevska,
Anna Jakubowska,
Helena Jernström,
Esther John,
Nichola Johnson,
Michael Jones,
Joseph Vijai,
Rudolf Kaaks,
Elza Khusnutdinova,
Cari Kitahara,
Stella Koutros,
Vessela Kristensen,
Allison W Kurian,
James Lacey,
Diether Lambrechts,
Loic Le Marchand,
Flavio Lejbkowicz,
Annika Lindblom,
Sibylle Loibl,
Adriana Lori,
Jan Lubinski,
Arto Mannermaa,
Mehdi Manoochehri,
Dimitrios Mavroudis,
Usha Menon,
AnnaMarie Mulligan,
Rachel Murphy,
Ines Nevelsteen,
William G Newman,
Nadia Obi,
Katie O'Brien,
Ken Offit,
Andrew Olshan,
Dijana Plaseska-Karanfilska,
Janet Olson,
Salvatore Panico,
Tjoung-Won Park-Simon,
Alpa Patel,
Paolo Peterlongo,
Brigitte Rack,
Paolo Radice,
Gad Rennert,
Valerie Rhenius,
Atocha Romero,
Emmanouil Saloustros,
Dale Sandler,
Marjanka K Schmidt,
Lukas Schwentner,
Mitul Shah,
Priyanka Sharma,
Jacques Simard,
Melissa Southey,
Jennifer Stone,
William J Tapper,
Jack Taylor,
Lauren Teras,
Amanda E Toland,
Melissa Troester,
Thérèse Truong,
Lizet E van der Kolk,
Clarice Weinberg,
Camilla Wendt,
Xiaohong Rose Yang,
Wei Zheng,
Argyrios Ziogas,
Alison M Dunning,
Paul Pharoah,
Douglas F Easton,
Shay Ben-Sachar,
Naama Elefant,
Ron Shamir,
Ran Elkon
Abstract
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.
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.
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).
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.