Citations 3
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.
The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
Moghadasi, Setareh , Vreeswijk, Maaike P.G. , Janssen, Linda AM, Borg, Åke , Ehrencrona, Hans , Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara , Engel, Christoph , Gehrig, Andrea, Hansen, Thomas van Overeem , Thomassen, Mads , Jensen, Uffe Birk , Kruse, Torben A., Ejlertsen, Bent , Gerdes, Anne‐Marie , Pedersen, Inge Søkilde , Caputo, Sandrine M. , Couch, Fergus J., Hallberg, Emily J., Ouweland, Ans MW van den, Collée, Margriet J., Teugels, Erik , Adank, Muriel A. , Luijt, Rob B. van der , Mensenkamp, Arjen R. , Oosterwijk, Jan C., Blok, Marinus J. , Janin, Nicolas, Claes, Kathleen , Tucker, Kathy , Viassolo, Valeria , Eccles, Diana , Devilee, Peter , Asperen, Christi J. van , Goldgar, David E., Gómez, E. , Meeks, Huong , Janssen, Linda A.M., Arnold, Norbert , Collée, Margriet , Toland, Amanda Ewart , Spurdle, Amanda B. , Eccles, Diana , Vreeswijk, Maaike P G , Claes, Kathleen B M , Ehrencrona, Hans , van der Luijt, Rob B , Engel, Christoph , van Asperen, Christi J , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Devilee, Peter
Journal of Medical Genetics | May 11, 2017 | Volume: 55 | Issue: 1 | Pages: 15-20
Background We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers. Methods Data were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. Results In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83). Conclusion Our results confirm that BRCA1*R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history.
Rare variants in XRCC2 as breast cancer susceptibility alleles: Table 1
Hilbers, Florentine , Hoogerbrugge, Nicoline, Oosterwijk, Jan C., Collée, Margriet J., Peterlongo, Paolo , Radice, Paolo , Manoukian, Siranoush , Feroce, Irène , Capra, F, Guidugli, Lucia, Offit, Kenneth, Shah, Sohela, Campbell, Ian , Thompson, Ella R. , James, Paul A. , Trainer, Alison H., Gracia, Javier, Devilee, Peter , Hoogerbrugge, Nicoline , Wijnen, Juul , Hoogerbrugge, Nicoline, Collée, Margriet , Couch, Fergus J. , Wang, Xianshu , Benı́tez, Javier , Asperen, Christi J. van , James, Paul , Peterlongo, Paolo , Radice, Paolo , Campbell, Ian G , Devilee, Peter , Manoukian, Siranoush
Journal of Medical Genetics | October 10, 2012 | Volume: 49 | Issue: 10 | Pages: 618-620
Background Recently, rare germline variants in XRCC2 were detected in non-BRCA1/2 familial breast cancer cases, and a significant association with breast cancer was reported. However, the breast cancer risk associated with these variants needs further evaluation. Methods The coding regions and exon–intron boundaries of XRCC2 were scanned for mutations in an international cohort of 3548 non-BRCA1/2 familial breast cancer cases and 1435 healthy controls using various mutation scanning methods. Predictions on functional relevance of detected missense variants were obtained from three different prediction algorithms. Results The only protein-truncating variant detected was found in a control. Rare non-protein-truncating variants were detected in 20 familial cases (0.6%) and nine healthy controls (0.6%). Although the number of variants predicted to be damaging or neutral differed between prediction algorithms, in all instances these categories were evenly represented among cases and controls. Conclusions Our data do not confirm an association between XRCC2 variants and breast cancer risk, although a relative risk smaller than two could not be excluded. Variants in XRCC2 are unlikely to explain a substantial proportion of familial breast cancer.