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

Levi, Hagai ; Michailidou, Kyriaki ; Ahearn, Thomas ; Andrulis, Irene L ; Anton-Culver, Hoda ; Antoniou, Antonis C ; Arndt, Volker ; Augustinsson, Annelie LU ; Bermisheva, Marina and Bodelon, Clara , et al. (2023) In Journal of Medical Genetics 60(12). p.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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medical Genetics
volume
60
issue
12
pages
12 pages
publisher
BMJ Publishing Group
external identifiers
  • pmid:37451831
  • scopus:85171799066
ISSN
0022-2593
DOI
10.1136/jmg-2023-109185
language
English
LU publication?
yes
additional info
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
id
e91a61bb-96be-4ae7-a439-0997f2be0df6
date added to LUP
2023-11-11 15:59:08
date last changed
2025-05-08 07:21:06
@article{e91a61bb-96be-4ae7-a439-0997f2be0df6,
  abstract     = {{<p>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.</p><p>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.</p><p>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).</p><p>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.</p>}},
  author       = {{Levi, Hagai and Michailidou, Kyriaki and Ahearn, Thomas and Andrulis, Irene L and Anton-Culver, Hoda and Antoniou, Antonis C and Arndt, Volker and Augustinsson, Annelie and Bermisheva, Marina and Bodelon, Clara and Bogdanova, Natalia V and Bojesen, Stig E and Brenner, Hermann and Byers, Helen and Dossus, Laure and Eccles, Diana M and Eliassen, A Heather and Eriksson, Mikael and Evans, Gareth and Fasching, Peter and Hall, Per and Jernström, Helena and Elkon, Ran}},
  issn         = {{0022-2593}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{12}},
  pages        = {{1186--1197}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Journal of Medical Genetics}},
  title        = {{Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel}},
  url          = {{http://dx.doi.org/10.1136/jmg-2023-109185}},
  doi          = {{10.1136/jmg-2023-109185}},
  volume       = {{60}},
  year         = {{2023}},
}