Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt


  • Fulltext

    Forlagets udgivne version, 833 KB, PDF-dokument

  • 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
  • Bojesen, Stig Egil
  • 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
  • Henrik Flyger
  • The BCAC Consortium
  • NBCS Collaborators
  • CTS Consortium
  • ABCTB Investigators
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.
TidsskriftJournal of Medical Genetics
Udgave nummer12
Antal sider12
StatusUdgivet - 2023

Bibliografisk note

Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

ID: 368621659