Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel Journal Article
| Authors: | Levi, H.; Carmi, S.; Rosset, S.; Yerushalmi, R.; Zick, A.; Yablonski-Peretz, T.; The BCAC Consortium; Wang, Q.; Bolla, M. K.; Dennis, J.; Michailidou, K.; Lush, M.; Ahearn, T.; Andrulis, I. L.; Anton-Culver, H.; Antoniou, A. C.; Arndt, V.; Augustinsson, A.; Auvinen, P.; Freeman, L. B.; Beckmann, M.; Behrens, S.; Bermisheva, M.; Bodelon, C.; Bogdanova, N. V.; Bojesen, S. E.; Brenner, H.; Byers, H.; Camp, N.; Castelao, J.; Chang-Claude, J.; Chirlaque, M. D.; Chung, W.; Clarke, C.; NBCS Collaborators; Collee, M. J.; Colonna, S.; CTS Consortium; Couch, F.; Cox, A.; Cross, S. S.; Czene, K.; Daly, M.; Devilee, P.; Dork, T.; Dossus, L.; Eccles, D. M.; Heather Eliassen, A.; Eriksson, M.; Evans, G.; Fasching, P.; Fletcher, O.; Flyger, H.; Fritschi, L.; Gabrielson, M.; Gago-Dominguez, M.; García-Closas, M.; Garcia-Saenz, J. A.; Genkinger, J.; Giles, G. G.; Goldberg, M.; Guénel, P.; Hall, P.; Hamann, U.; He, W.; Hillemanns, P.; Hollestelle, A.; Hoppe, R.; Hopper, J.; ABCTB Investigators; Jakovchevska, S.; Jakubowska, A.; Jernström, H.; John, E.; Johnson, N.; Jones, M.; Vijai, J.; Kaaks, R.; Khusnutdinova, E.; Kitahara, C.; Koutros, S.; Kristensen, V.; Kurian, A. W.; Lacey, J.; Lambrechts, D.; Le Marchand, L.; Lejbkowicz, F.; Lindblom, A.; Loibl, S.; Lori, A.; Lubinski, J.; Mannermaa, A.; Manoochehri, M.; Mavroudis, D.; Menon, U.; Mulligan, A.; Murphy, R.; Nevelsteen, I.; Newman, W. G.; Obi, N.; O’Brien, K.; Offit, K.; Olshan, A.; Plaseska-Karanfilska, D.; Olson, J.; Panico, S.; Park-Simon, T. W.; Patel, A.; Peterlongo, P.; Rack, B.; Radice, P.; Rennert, G.; Rhenius, V.; Romero, A.; Saloustros, E.; Sandler, D.; Schmidt, M. K.; Schwentner, L.; Shah, M.; Sharma, P.; Simard, J.; Southey, M.; Stone, J.; Tapper, W. J.; Taylor, J.; Teras, L.; Toland, A. E.; Troester, M.; Truong, T.; van der Kolk, L. E.; Weinberg, C.; Wendt, C.; Yang, X. R.; Zheng, W.; Ziogas, A.; Dunning, A. M.; Pharoah, P.; Easton, D. F.; Ben-Sachar, S.; Elefant, N.; Shamir, R.; Elkon, R. |
| Article Title: | Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel |
| 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. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. |
| Keywords: | adult; controlled study; middle aged; major clinical study; single nucleotide polymorphism; genetics; genetic predisposition to disease; breast cancer; cohort analysis; genome-wide association study; risk factors; transcription factor; breast neoplasms; brca1 protein; brca2 protein; risk factor; transcription factors; consanguinity; breast tumor; israel; genetic predisposition; jews; jew; gene linkage disequilibrium; multifactorial inheritance; humans; human; female; article; evaluation study; genetic distance; genetic risk score; cross validation |
| Journal Title: | Journal of Medical Genetics |
| Volume: | 60 |
| Issue: | 12 |
| ISSN: | 0022-2593 |
| Publisher: | BMJ Publishing Group Ltd. |
| Date Published: | 2023-12-01 |
| Start Page: | 1186 |
| End Page: | 1197 |
| Language: | English |
| DOI: | 10.1136/jmg-2023-109185 |
| PUBMED: | 37451831 |
| PROVIDER: | scopus |
| PMCID: | PMC10715538 |
| DOI/URL: | |
| Notes: | Article -- MSK author Vijai Joseph's first and last names are reversed on the original publication -- Source: Scopus |
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