Citations 2
Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel
Yerushalmi, Rinat , Yablonski‐Peretz, Tamar, Wang, Qin , Bolla, Manjeet K. , Michailidou, Kyriaki , Ahearn, Thomas U. , Andrulis, Irene L. , Antoniou, Antonis C. , Auvinen, Päivi , Freeman, Laura Beane, Beckmann, Matthias W. , Bermisheva, Marina , Bodelón, Clara , Bogdanova, Natalia , Bojesen, Stig E. , Byers, Helen, Camp, Nicola J. , Chang‐Claude, Jenny , Chirlaque, María‐Dolores , Collaborators, NBCS, Collée, Margriet J., Dörk, Thilo , Eccles, Diana , Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Goldberg, Mark S. , Guénel, Pascal , Hamann, Ute, He, Wei , Hillemanns, Peter , Hoppe, Reiner , Hopper, John L. , Investigators, ABCTB, Jakovchevska, Simona, John, Esther M. , Johnson, Nichola , Jones, Michael E. , Kristensen, Vessela N. , Kurian, Allison W. , Lambrechts, Diether , Lejbkowicz, Flavio, Lindblom, Annika , Loibl, Sibylle , Lori, Adriana , Mannermaa, Arto, Manoochehri, Mehdi, Mavroudis, Dimitrios, Menon, Usha , Nevelsteen, Ines, Obi, Nadia , Offit, Ken, Plaseska‐Karanfilska, Dijana , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Rack, Brigitte , Rhenius, Valerie , Romero, Atocha , Schwentner, Lukas , Shah, Mitul , Stone, Jennifer , Taylor, Jack A. , Kolk, Lizet E. van der, Wendt, Camilla, Yang, Xiaohong R. , Zheng, Wei , Pharoah, Paul D.P. , Easton, Douglas F. , Ben-Sachar, Shay, Elefant, Naama , Shamir, Ron , Elkon, Ran , Lambrechts, Diether , Michailidou, Kyriaki , Antoniou, Antonis C , Devilee, Peter , Eccles, Diana , Newman, William G , Radice, Paolo , Elkon, Ran , Dörk, Thilo , Lambrechts, Diether , Hillemanns, Peter , Pharoah, Paul D P , Menon, Usha , Evans, D Gareth , John, Esther M , Jones, Michael E , Lambrechts, Diether , Guénel, Pascal , Romero, Atocha , García-Closas, Montserrat , Bogdanova, Natalia V , Taylor, Jack A , Zheng, Wei , Kurian, Allison W , Stone, Jennifer , Bojesen, Stig E , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Levi, Hagai , Carmi, Shai , Rosset, Saharon , Zick, Aviad , Dennis, Joe , Lush, Michael J. , Anton‐Culver, Hoda , Arndt, Volker , Augustinsson, Annelie , Behrens, Sabine , Brenner, Hermann , Castelao, Jose E. , Chung, Wendy K. , Clarke, Christine L. , Collaborators, NBCS, Collée, Margriet , Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Daly, Mary Beryl , Devilee, Peter , Dossus, Laure , Eliassen, A. Heather , Eriksson, Mikael , Fletcher, Olivia , Fritschi, Lin , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Giles, Graham G. , Hall, Per N , Hollestelle, Antoinette , Investigators, ABCTB, Jakubowska, Anna , Jernström, Helena , Vijai, Joseph , Kaaks, Rudolf , Хуснутдинова, Э. К. , Kitahara, Cari M. , Koutros, Stella , Lacey, James V. , Marchand, Loı̈c Le , Lubiński, Jan , Mannermaa, Arto, Mulligan, Anna Marie , Murphy, Rachel A. , Newman, William G. , O’Brien, Katie M. , Olshan, Andrew F. , Olson, Janet E. , Panico, Salvatore , Peterlongo, Paolo , Radice, Paolo , Rennert, Gad , Saloustros, Emmanouil , Sandler, Dale P. , Schmidt, Marjanka K. , Sharma, Priyanka , Simard, Jacques , Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Toland, Amanda Ewart , Troester, Melissa A. , Truong, Thérèse , Weinberg, Clarice R. , Ziogas, Argyrios , Dunning, Alison M.
Journal of Medical Genetics | July 14, 2023 | Volume: 60 | Issue: 12 | Pages: 1186-1197
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.
Rare Copy Number Variants (CNVs) and Breast Cancer Risk
Dorling, Leila , Bola, Manjeet, Wang, Qin , Andrulis, Irene L. , Antonenkova, Natalia, Aronson, Kristan J. , Freeman, Laura Beane, Beckmann, Matthias W. , Bojeson, Stig, Chang‐Claude, Jenny , Chenevix‐Trench, Georgia , Collaborators, NBCS, Collée, J. Margriet, Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, Hahen, Eric, Haiman, Christopher A. , Hoppe, Reine, Investigators, ACTB, Investigators, kConFab, Jager, Agnes , Johnson, Nichola , Keeman, Renske , Ko, Yon‐Dschun, Kosma, Veli‐Matti , Kristensen, Vessela N. , Kubelka‐Sabit, Katerina , Kurian, Alison, Larson, Nicole L. , Linet, Martha S. , Łukomska, Alicja, Mannermaa, Arto , Mavroudis, Dimitrios, Park‐Simon, Tjoung‐Won , Peterlongo, Paolo , Plaseska-Karanfilska, Dijana, Sawyer, Elinor J. , Schmutzler, Rita K., Shibli, Rana , Soucy, Penny, Tomlinson, Ian , Vachon, Celine M. , Wendt, Camilla, Yang, Xiaohong R. , Easton, Douglas F. , Peterlongo, Paolo , Evans, D Gareth , Chenevix-Trench, Georgia , Sawyer, Elinor J , Dennis, Joe , Tyrer, Jonathan P. , Walker, Logan C. , Michailidou, Kyriaki , Ahearn, Thomas U. , Anton‐Culver, Hoda , Arndt, Volker , Behrens, Sabine , Benı́tez, Javier , Bermisheva, Marina , Bojesen, Stig E. , Brenner, Hermann , Castelao, Jose E. , Clarke, Christine L. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Devilee, Peter , Dörk, Thilo , Dossus, Laure , Eliassen, A. Heather , Eriksson, Mikael , Figueroa, Jonine D. , Fletcher, Olivia , Fritschi, Lin , Gabrielson, Marike , Gago-Domínguez, Manuela , García‐Closas, Montserrat , Giles, Graham G. , González‐Neira, Anna , Guénel, Pascal , Hall, Per N , Hollestelle, Antoinette , Hoppe, Reiner , Hopper, John L. , Howell, Anthony , Jakubowska, Anna , John, Esther M. , Jones, Michael E. , Jung, Audrey , Kaaks, Rudolf , Хуснутдинова, Э. К. , Kitahara, Cari M. , Koutros, Stella , Kraft, Peter , Lambrechts, Diether , Manoukian, Siranoush , Margolin, Sara , Milne, Roger L. , Muranen, Taru , Murphy, Rachel A. , Nevanlinna, Heli , Olson, Janet E. , Olsson, Håkan , Perou, Charles M. , Pylkäs, Katri , Rennert, Gad , Saloustros, Emmanouil , Sandler, Dale P. , Schmidt, Marjanka K. , Smeets, Ann , Southey, Melissa C. , Swerdlow, Anthony J. , Tamimi, Rulla M. , Taylor, Jack A. , Teras, Lauren R. , Terry, Mary Beth , Troester, Melissa A. , Truong, Thérèse , Vachon, Celine M. , Wendt, Camilla, Winqvist, Robert , Wolk, Alicja , Zheng, Wei , Ziogas, Argyrios , Simard, Jacques , Dunning, Alison M. , Pharoah, Paul D.P.
No container title available | June 22, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract BackgroundCopy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data.ResultsGene burden tests detected the strongest association for deletions in BRCA1 (P= 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P= 0.0008), ATM (P= 0.002) and BRCA2 (P= 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci.ConclusionsThis is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.