Citations 14
Threshold-Based Overlap of Breast Cancer High-Risk Classification Using Family History, Polygenic Risk Scores, and Traditional Risk Models in 180,398 Women
Ho, Peh Joo , Loo, Christine Kim Yan , Lim, Ryan Jak Yang, Goh, Mui Heng, Abubakar, Mustapha , Ahearn, Thomas U. , Andrulis, Irene L. , Antonenkova, Natalia, Aronson, Kristan J. , Augustinsson, Annelie , Behrens, Sabine , Bodelón, Clara , Bogdanova, Natalia , Bolla, Manjeet K. , Brantley, Kristen D. , Brenner, Hermann , Byers, Helen L., Camp, Nicola J. , Cessna, Melissa H., Chang-Claude, Jenny, Choi, Ji-Yeob , Czene, Kamila , Dörk, Thilo , Eliassen, A. Heather , Engel, Christoph , Eriksson, Mikael , Evans, D. Gareth , Fritschi, Lin , Genkinger, Jeanine M. , Geurts-Giele, Willemina R.R. , Glendon, Gord, Hall, Per , Hamann, U. , Ho, Cecilia Y.S., Hooning, Maartje J. , Hoppe, Reiner , Humphreys, Keith , Ito, Hidemi , Jakubowska, Anna , Jernström, Helena , John, Esther M. , Johnson, Nichola , Kang, Daehee , Kim, Sung‐Won , Kitahara, Cari M. , Ko, Yon-Dschun, Kraft, Peter, Kwong, Ava , Lambrechts, Diether, Larsson, Susanna C. , Li, Shuai , Lindblom, Annika , Linet, Martha, Lissowska, Jolanta , Lophatananon, Artitaya , MacInnis, Robert J. , Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Matsuo, Keitaro , Michailidou, Kyriaki , Taib, Nur Aishah Mohd , Murphy, Rachel A. , Newman, William G. , Obi, Nadia , Olopade, Olufunmilayo I., Panayiotidis, Mihalis I. , Park, Sue K. , Park‐Simon, Tjoung‐Won , Patel, Alpa V , Peterlongo, Paolo , Plaseska‐Karanfilska, Dijana , Pylkäs, Katri , Rashid, Muhammad Usman , Rodríguez, Juan , Sandler, Dale P. , Sawyer, Elinor J. , Scott, Christopher G. , Shahi, Shamim , Shu, Xiao‐Ou , Shulman, Katerina, Simard, Jacques , Southey, Melissa C., Stone, Jennifer , Taylor, Jack A. , Teo, Soo‐Hwang , Teras, Lauren R. , Vachon, Celine M., Houdt, Maxime Van , Verhoeven, Jelle , Weinberg, Clarice R. , Wolk, Alicja , Yamaji, Taiki , Yip, Cheng Har , Zheng, Wei , Hartman, Mikael , Li, Jingmei , Investigators, on behalf of the ABCTB, Investigators, kConFab, Investigators, MyBrCa, Investigators, SGBCC, Olopade, Olufunmilayo I. , Lambrechts, Diether , Lambrechts, Diether , Hamann, Ute , Hooning, Maartje J. , Bogdanova, Natalia V , Czene, Kamila , Dörk, Thilo , Eliassen, A Heather , Engel, Christoph , Eriksson, Mikael , Evans, D Gareth , Fletcher, Olivia , Fritschi, Lin , Genkinger, Jeanine , Hall, Per N , Ho, Cecilia Y S , Humphreys, Keith , Ito, Hidemi , Jakubowska, Anna , Jernström, Helena , Johnson, Nichola , Kim, Sung-Won , Kitahara, Cari M , Kwong, Ava , Larsson, Susanna C , Li, Shuai , Lindblom, Annika , Lissowska, Jolanta , Lophatananon, Artitaya , Maclnnis, Robert , Matsuo, Keitaro , Michailidou, Kyriaki , Mohd Taib, Nur Aishah , Murphy, Rachel A , Newman, William G , Obi, Nadia , Panayiotidis, Mihalis I , Park, Sue K , Park-Simon, Tjoung-Won , Peterlongo, Paolo , Plaseska-Karanfilska, Dijana , Pylkäs, Katri , Rashid, Muhammad U , Rennert, Gad , Rodriguez, Juan , Sandler, Dale P , Sawyer, Elinor J , Scott, Christopher , Shu, Xiao-Ou , Simard, Jacques , Stone, Jennifer , Taylor, Jack A , Teo, Soo H , Teras, Lauren R , Houdt, Maxime Van , Verhoeven, Jelle , Weinberg, Clarice R , Wolk, Alicja , Zheng, Wei , Hartman, Mikael , Li, Jingmei , Lambrechts, Diether , Behrens, Sabine , John, Esther M , Olopade, Olufunmilayo I , Lambrechts, Diether , Augustinsson, Annelie , Brenner, Hermann , Camp, Nicola J , Brantley, Kristen D , Lim, Ryan Jak Yang, Byers, Helen, Castelao, Jose E. , Chang‐Claude, Jenny , Chanock, Stephen Jacob , Chenevix‐Trench, Georgia , Colonna, Sarah V. , Daly, Mary Beryl , Derouane, Françoise , Fletcher, Olivia , Gago-Domínguez, Manuela , Ho, Weang-Kee , Howell, Anthony , Iwasaki, Motoki , Ko, Yon‐Dschun, Mannermaa, Arto , Manoukian, Siranoush , Margolin, Sara , Milne, Roger L. , Muir, Kenneth , O’Brien, Katie M. , Rennert, Gad , Saloustros, Emmanouil , Southey, Melissa C. , Terry, Mary Beth , Torres, Diana , Investigators, on behalf of the ABCTB, Investigators, kConFab, Investigators, MyBrCa, Investigators, SGBCC
Cancers | November 3, 2025 | Volume: 17 | Issue: 21 | Pages: 3561
Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case–control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62–1.64, AUC = 0.551–0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94–0.99, AUC = 0.523–0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations.
Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium
Morra, Anna , Jung, Audrey , Behrens, Sabine , Keeman, Renske , Ahearn, Thomas U. , Arndt, Volker , Augustinsson, Annelie , Auvinen, Päivi , Becher, Heiko , Beckmann, Matthias W. , Bojesen, Stig E. , Bolla, Manjeet K. , Brenner, Hermann , Camp, Nicola J. , Campa, Daniele , Castelao, Jose E. , Choi, Ji‐Yeob , Cox, Angela , Easton, Douglas F. , Eccles, Diana M., Egan, Kathleen M. , Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, Gago-Domínguez, Manuela , Gapstur, Susan M. , Gaudet, Mia M. , Grip, Mervi, Guénel, Pascal , Haiman, Christopher A. , Håkansson, Niclas , Hamann, Ute, Hartman, Mikael , Heyworth, Jane , Hoppe, Reiner , Hopper, John L. , Hunter, David J. , Jager, Agnes , Jakimovska, Milena , Janni, Wolfgang , Koutros, Stella , Kristensen, Vessela N. , Lambrechts, Diether , Li, Jingmei , Lindblom, Annika , Mannermaa, Arto , Manoochehri, Mehdi, Margolin, Sara , Mariapun, Shivaani, Mavroudis, Dimitrios, Muranen, Taru , Newman, William G. , Noh, Dong‐Young , Nordestgaard, Børge G. , Obi, Nadia , Olsson, Håkan , Park‐Simon, Tjoung‐Won , Petridis, Christos , Plaseska‐Karanfilska, Dijana , Rashid, Muhammad Usman , Rennert, Gad , Rennert, Gad , Rhenius, Valerie , Romero, Atocha , Saloustros, Emmanouil , Sawyer, Elinor J. , Schneeweiß, Andreas , Schwentner, Lukas , Shah, Mitul , Shen, Chen‐Yang , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Torres, Diana , Vachon, Celine M. , Wang, Qin , Wang, Sophia , Williams, Justin A. , Winqvist, Robert , Wu, Anna H. , Yoo, Keun-Young, Yu, Jyh‐Cherng , Zheng, Wei , Yang, Xiaohong R. , Eliassen, A. Heather , García‐Closas, Montserrat , Teo, Soo‐Hwang , Chang‐Claude, Jenny , Eccles, Diana , Khaw, Kay‐Tee , Lambrechts, Diether , Arndt, Volker , Augustinsson, Annelie , Brenner, Hermann , Camp, Nicola J , Canzian, Federico , Cox, Angela , Dunning, Alison M , Evans, D Gareth , Fasching, Peter A , Gago-Dominguez, Manuela , García-Sáenz, José A , Gaudet, Mia M , Giles, Graham G , Guénel, Pascal , Hall, Per N , Hart, Steven N , Hartman, Mikael , Ito, Hidemi , Jager, Agnes , Jakubowska, Anna , Janni, Wolfgang , Kaaks, Rudolf , Kapoor, Pooja Middha , Koutros, Stella , Lambrechts, Diether , Li, Jingmei , Matsuo, Keitaro , Milne, Roger L , Muranen, Taru A , Newman, William G , Park-Simon, Tjoung-Won , Pharoah, Paul D P , Rennert, Gad , Rennert, Gad , Rhenius, Valerie , Romero, Atocha , Saloustros, Emmanouil , Schneeweiss, Andreas , Scott, Christopher , Southey, Melissa C , Stram, Daniel O. , Tamimi, Rulla M , Tomlinson, Ian , Torres, Diana , Vachon, Celine M. , Wolk, Alicja , Ziogas, Argyrios , Holmes, Michelle D , García-Closas, Montserrat , Teo, Soo H , Schmidt, Marjanka K , Chang-Claude, Jenny , Lambrechts, Diether , Behrens, Sabine , Eccles, Diana , Keeman, Renske , Zheng, Wei , Wang, Sophia S , Jung, Audrey Y , Becher, Heiko , Eliassen, A Heather , Håkansson, Niclas , Rashid, Muhammad U , Bojesen, Stig E , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Anton‐Culver, Hoda , Freeman, Laura E. Beane , Blomqvist, Carl , Briceño, Ignacio , Brucker, Sara Yvonne , Canzian, Federico , Chanock, Stephen Jacob , Clarke, Christine L. , Couch, Fergus J. , Cross, Simon S. , Czene, Kamila , Dörk, Thilo , Dunning, Alison M. , Dwek, Miriam , García-Sáenz, José Á. , Giles, Graham G. , Han, Sileny , Hart, Steven N. , Ito, Hidemi , Jakubowska, Anna , Kaaks, Rudolf , Kang, Daehee , Middha, Pooja , Kitahara, Cari M. , Kraft, Peter , Lacey, James V. , Marchand, Loı̈c Le , Lubiński, Jan , Lush, Michael J. , Manoochehri, Mehdi, Matsuo, Keitaro , Milne, Roger L. , Olshan, Andrew F. , Pharoah, Paul D.P. , Presneau, Nadège , Scott, Christopher G. , Shu, Xiao‐Ou , Southey, Melissa C. , Tamimi, Rulla M. , Tapper, William , Troester, Melissa A. , Truong, Thérèse , Wolk, Alicja , Ziogas, Argyrios , Schmidt, Marjanka K.
Cancer Epidemiology, Biomarkers & Prevention | January 26, 2021 | Volume: 30 | Issue: 4 | Pages: 623-642
Abstract Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72–0.86)]; >0–<5 years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)]; ever versus never use of oral contraceptives [0.91 (0.87–0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02–1.21) for current versus never smoking. Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status
Feng, Helian , Gusev, Alexander , Wu, Lang , Abu-Full, Zomoroda, Aittomäki, Kristiina, Andrulis, Irene L. , Antoniou, Antonis C. , Arason, Aðalgeir , Arndt, Volker , Aronson, Kristan J. , Asseryanis, Ella, Auer, Paul L. , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barrowdale, Daniel , Beckmann, Matthias W. , Bermisheva, Marina , Białkowska, Katarzyna , Bogdanova, Natalia , Bojesen, Stig E. , Bolla, Manjeet K. , Borg, Åke , Brauch, Hiltrud , Brenner, Hermann , Brüning, Thomas , Burwinkel, Barbara , Caldés, Trinidad , Canisius, Sander , Campa, Daniele , Carter, Brian D., Castelao, Jose E. , Chang‐Claude, Jenny , Christiansen, Hans , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Cox, Angela , Daly, Mary B., Leeneer, Kim De , Dörk, Thilo , Dwek, Miriam , Eccles, Diana M., Ejlertsen, Bent , Engel, Christoph , Fasching, Peter A. , Flyger, Henrik, Friedman, Eitan , Frost, Debra, Gabrielson, Marike , Ganz, Patricia A. , Gapstur, Susan M. , García‐Closas, Montserrat , Gaudet, Mia M. , Glendon, Gord , Goldberg, Mark S. , Goldgar, David E., González‐Neira, Anna , Greene, Mark H. , Guénel, Pascal , Haiman, Christopher A. , Hamann, Ute, Hake, Christopher R., He, Wei , Heyworth, Jane , Hogervorst, Frans B.L., Hooning, Maartje J. , Hoover, Robert N. , Hopper, John L. , Huang, Guanmengqian, Hulick, Peter J. , Humphreys, Keith , Imyanitov, Evgeny N., Investigators, ABCTB, Investigators, HEBON, Investigators, BCFR, Investigators, OCGN, Jakimovska, Milena , Jakubowska, Anna , James, Paul A. , Janavicius, Ramunas, Jankowitz, Rachel C. , John, Esther M. , Johnson, Nichola , Jung, Audrey , Kiiski, Johanna I. , Konstantopoulou, Irene , Kristensen, Vessela N. , Laitman, Yael , Lambrechts, Diether , Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne , Lindor, Noralane M. , Lindström, Sara, Lo, Wing‐Yee, Loud, Jennifer T. , Makalic, Enes , Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush , Margolin, Sara , Matricardi, Laura , Maurer, Tabea, Mavroudis, Dimitrios, McGuffog, Lesley, Meindl, Alfons , Menon, Usha , Michailidou, Kyriaki , Kapoor, Pooja M., Montagna, Marco , Moreno, Fernando , Muranen, Taru , Nathanson, Katherine L. , Nevelsteen, Ines, Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Olsson, Håkan , Osório, Ana , Papp, J., Park‐Simon, Tjoung‐Won , Pedersen, Inge Søkilde , Peixoto, Ana , Peterlongo, Paolo , Peto, Julian , Phillips, Kelly‐Anne , Plaseska‐Karanfilska, Dijana , Poppe, Bruce , Pradhan, Nisha , Prajzendanc, Karolina , Punie, Kevin , Pylkäs, Katri , Rantala, Johanna, Rashid, Muhammad Usman , Rennert, Gad , Romero, Atocha , Saloustros, Emmanouil , Sandler, Dale P. , Santos, Catarina , Sawyer, Elinor J. , Schmutzler, Rita K., Schoemaker, Minouk J. , Scott, Rodney J. , Simard, Jacques , Skytte, Anne‐Bine , Soucy, Penny, Spinelli, John J. , Stone, Jennifer , Tapper, William , Taylor, Jack A. , Teixeira, Manuel R. , Terry, Mary Beth , Teulé, Àlex , Thomassen, Mads , Thöne, Kathrin , Thull, Darcy L. , Tollenaar, Rob A.�E.�M. , Torres, Diana , Vachon, Celine M. , Ouweland, Ans M.W. van den, Vega, Ana , Viel, Alessandra , Vieiro‐Balo, Paula, Wang, Qin , Wappenschmidt, Barbara , Weinberg, Clarice R. , Weitzel, Jeffrey N. , Wendt, Camilla, Winqvist, Robert , Yang, Xiaohong R., Easton, Douglas F. , Chenevix‐Trench, Georgia , Durocher, Francine , Eccles, Diana , Janavičius, Ramūnas , Khaw, Kay‐Tee , Lambrechts, Diether , Lindor, Noralane, Dörk, Thilo , Lambrechts, Diether , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Rennert, Gad , Sandler, Dale P , Teixeira, Manuel R , Eccles, Diana , Menon, Usha , Vega, Ana , Weitzel, Jeffrey N , Claes, Kathleen B M , Azzollini, Jacopo , John, Esther M , Konstantopoulou, Irene , Matricardi, Laura , Olopade, Olufunmilayo I , Arndt, Volker , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , Muranen, Taru A , Romero, Atocha , Saloustros, Emmanouil , Torres, Diana , García-Closas, Montserrat , Makalic, Enes , Michailidou, Kyriaki , Bogdanova, Natalia V , Taylor, Jack A , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Engel, Christoph , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Jung, Audrey Y , Gabrielson, Marike , Stone, Jennifer , Pylkäs, Katri , Rashid, Muhammad U , De Leeneer, Kim , Manoukian, Siranoush , Bojesen, Stig E , Schoemaker, Minouk J , Weinberg, Clarice R , Phillips, Kelly-Anne , Terry, Mary Beth , Brauch, Hiltrud , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Paşaniuc, Bogdan , Long, Jirong , Anton‐Culver, Hoda , Arun, Banu , Balmañà, Judith , Barnes, Daniel R. , Behrens, Sabine , Benı́tez, Javier , Blanco, Ana , Blomqvist, Carl , Boeckx, Bram , Bonanni, Bernardo , Borg, Åke , Briceño, Ignacio , Broeks, Annegien , Cai, Qiuyin , Caligo, Maria A. , Campbell, Ian , Carter, Jonathan , Chanock, Stephen Jacob , Chung, Wendy K. , Clarke, Christine L. , Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Couch, Fergus J. , Cross, Simon S. , Cybulski, Cezary , Czene, Kamila , Hoya, Miguel de la , Dennis, Joe , Devilee, Peter , Dı́ez, Orland , Domchek, Susan M. , dos‐Santos‐Silva, Isabel , Dunning, Alison M. , Ellberg, Carolina , Eriksson, Mikael , Fletcher, Olivia , Fostira, Florentia , Fritschi, Lin , Garber, Judy E. , García-Sáenz, José Á. , Giles, Graham G. , Godwin, Andrew K. , Goldgar, David E., Gronwald, Jacek , Hall, Per N , Hollestelle, Antoinette , Investigators, ABCTB, Investigators, HEBON, Investigators, BCFR, Investigators, OCGN, Isaacs, Claudine , Vijai, Joseph , Karlan, Beth Y. , Хуснутдинова, Э. К. , Lázaro, Conxi , Leslie, Goska , Lubiński, Jan , Mannermaa, Arto, Martens, John W.M. , Martı́nez, Marı́a Elena , Meindl, Alfons , Kapoor, Pooja M., Miller, Austin , Moserle, Lidia , Mulligan, Anna Marie , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Parsons, Michael T. , Pharoah, Paul D.P. , Presneau, Nadège , Radice, Paolo , Risch, Harvey A. , Robson, Mark E. , Schmidt, Marjanka K. , Schmidt, Daniel F. , Sharma, Priyanka , Shu, Xiao‐Ou , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Swerdlow, Anthony J. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Truong, Thérèse , Tung, Nadine , Vachon, Celine M. , Asperen, Christi J. van , Rensburg, Elizabeth J. van , Yannoukakos, Drakoulis , Ziogas, Argyrios , Milne, Roger L. , Zheng, Wei , Kraft, Peter , Jiang, Xia
Genetic Epidemiology | March 2, 2020 | Volume: 44 | Issue: 5 | Pages: 442-468
AbstractPrevious transcriptome‐wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome‐wide association studies (GWAS), but analyses of breast cancer subtype‐specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta‐analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case‐only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS‐significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast‐cancer gene in three of six regions harboring multiple TWAS‐significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer.
Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
Patel, Vivek , Busch, Evan L. , Cronin, Angel M., Leslie, Goska , McGuffog, Lesley, Adlard, Julian , Agata, Simona , Agnarsson, Bjarni A. , Ahmed, Munaza, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Arason, Aðalgeir , Artioli, Grazia, Arver, Brita, Auber, Bernd , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barroso, Alicia, Barrowdale, Daniel , Belotti, Muriel, Bertelsen, Birgitte , Blok, Marinus J. , Bodrogi, I., Bonadona, Valérie, Bondavalli, Davide , Boonen, Susanne E. , Borde, Julika , Borg, Åke , Bradbury, Angela R. , Brady, Angela, Brewer, Carole, Brunet, Joan , Buecher, Bruno , Caldés, Trinidad , Caliebe, Almuth , Calvello, Mariarosaria , Carrasco, Estela , Chan, Tsun Leung , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Cortesi, Laura , Daly, Mary B., Damante, Giuseppe , Darder, Esther , Davidson, Rosemarie, Puppa, Lara Della , Ding, Yuan Chun , Ditsch, Nina , Donaldson, Alan, Dworniczak, Bernd , Easton, Douglas F. , Eccles, Diana M., Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , Engel, Christoph , Evans, D. Gareth , Faivre, Laurence, Faust, Ulrike , Feliubadaló, Lídia , Foretová, Lenka , Fountzilas, George , Frost, Debra, García‐Barberán, Vanesa , Gauthier‐Villars, Marion , Géczi, Lajos , Gehrig, Andrea, Gesta, Paul , Giannini, Giuseppe , Glendon, Gord , Goldgar, David E. , Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hamann, Ute, Hauke, Jan , Herold, Natalie, Hogervorst, Frans B.L., Honisch, Ellen, Hulick, Peter J. , Investigators, kConFab, Investigators, Hebon, Izatt, Louise , Jager, Agnes , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Jensen, Thomas D., Johannsson, Oskar T., John, Esther M. , Kang, Eunyoung , Kast, Karin, Kiiski, Johanna I. , Kim, Sung-Won, Ko, Kwang‐Pil , Konstantopoulou, Irene , Kramer, Gero , Krogh, Lotte, Kruse, Torben A., Kwong, Ava , Larsen, Mirjam, Lasset, Christine , Lautrup, Charlotte Kvist , Lee, Jihyoun , Lee, Jong Won, Lee, Min Hyuk , Lesueur, Fabienne , Liljegren, Annelie , Lindblom, Annika , Llovet, Patricia , López‐Fernández, Adrià , López‐Perolio, Irene, Lorca, Víctor , Loud, Jennifer T. , S.K., Edmond , Mai, Phuong L., Manoukian, Siranoush , Mari, Véronique , Martin, Lynn , Matricardi, Laura , Mebirouk, Noura, Medici, Veronica, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Miller, Clare , Gomes, D. Molina , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Navrátilová, Marie , Niederacher, Dieter , Nielsen, Finn C., Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Ong, Kai-Ren, Osório, Ana , Ott, Claus‐Eric , Park, Sue K. , Pedersen, Inge Søkilde , Peissel, Bernard , Peixoto, Ana , Peterlongo, Paolo , Petersen, Annabeth Høgh , Porteous, Mary, Pujana, Miguel Ángel , Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rizzolo, Piera , Rookus, Matti A. , Rossing, Caroline Maria, Ruddy, Kathryn J. , Santos, Catarina , Saule, Claire , Scarpitta, Rosa , Schmutzler, Rita K., Schuster, Hélène, Senter, Leigha , Seynaeve, Caroline, Shah, Payal D. , Silvestri, Valentina , Simard, Jacques , Skytte, Anne‐Bine , Snape, Katie , Solano, Ángela R. , Soucy, Penny, Sunde, Lone , Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Teo, Soo‐Hwang , Thomassen, Mads , Tibiletti, Maria Grazia , Toland, Amanda Ewart, Torres, Diana , Trainer, Alison H., Baan, Frederieke H. van der , Kolk, Lizet E. van der, Hest, Liselotte P. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Viel, Alessandra , Vierstraete, Jeroen , Villa, Roberta, Wachenfeldt, Anna von , Wagner, Philipp , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Wieme, Greet , Yadav, Siddhartha , Yoon, Sook‐Yee , Zanzottera, Cristina , Zorn, Kristin K. , D’Amico, Anthony V. , Freedman, Matthew L. , Pomerantz, Mark M., Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Ottini, Laura , Nielsen, Henriette Roed, Durocher, Francine , Eccles, Diana , Caputo, Sandrine M. , Faivre, Laurence , Leslie, Goska , Adlard, Julian , Arnold, Norbert , Auber, Bernd , Azzollini, Jacopo , Barnes, Daniel R , Brunet, Joan , Caligo, Maria A , Campbell, Ian G , Claes, Kathleen B M , Darder, Esther , Dennis, Joe , Dworniczak, Bernd , Eeles, Rosalind A , Ehrencrona, Hans , Ejlertsen, Bent , Evans, D Gareth , Garre, Pilar , Greene, Mark H , Hulick, Peter J , Jager, Agnes , James, Paul , John, Esther M , Joseph, Vijai , Kim, Sung-Won , Konstantopoulou, Irene , Lesueur, Fabienne , Matricardi, Laura , Gomes, Denise Molina , Nevanlinna, H , Olopade, Olufunmilayo I , Palli, Domenico , Park, Sue K , Parsons, Michael T , Peterlongo, Paolo , Petersen, Annabeth Høgh , Pujana, Miquel Angel , Ruddy, Kathryn J , Scarpitta, Rosa , Shah, Payal D , Silvestri, Valentina , Southey, Melissa C , Spurdle, Amanda B , Stoppa-Lyonnet, Dominique , Sunde, Lone , Teixeira, Manuel R , Teo, Soo H , Tommasi, Stefania , Toss, Angela , van der Luijt, Rob B , Vierstraete, Jeroen , Wieme, Greet , Yadav, Siddhartha , Antoniou, Antonis C , Eccles, Diana , Weitzel, Jeffrey N , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Boonen, Susanne E , Cortesi, Laura , Engel, Christoph , Hahnen, Eric , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Senter, Leigha , Faivre, Laurence , Rashid, Muhammad U , Calvello, Mariarosaria , Feliubadaló, Lidia , Hauke, Jan , Manoukian, Siranoush , Pomerantz, Mark M , Kwong, Ava , Lindblom, Annika , Friebel, Tara M. , Arnold, Norbert , Balmañà, Judith , Barnes, Daniel R. , Benı́tez, Javier , Bonadona, Valérie , Bonanni, Bernardo , Borg, Åke , Buys, Saundra S. , Cabezas-Camarero, Santiago , Caligo, Maria A. , Campbell, Ian , Carnevali, Ileana Wanda , Chu, Annie Tsz-Wai , Chung, Wendy K. , Cook, Jackie A , Couch, Fergus J. , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Fostira, Florentia , Gerdes, Anne‐Marie , Godwin, Andrew K. , Herold, Natalie, Hopper, John L. , Jensen, Thomas Dyrso, Vijai, Joseph , Lasset, Christine , Lázaro, Conxi , Lemke, Johannes R. , Mai, Phuong L., Meindl, Alfons , Miller, Clare, Moserle, Lidia , Mulligan, Anna Marie , Nevanlinna, Heli , Palli, Domenico , Parsons, Michael T. , Perez-Segura, Pedro , Radice, Paolo , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Shin, Vivian Yvonne , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Steele, Linda, Steinemann, Doris , Stoppa‐Lyonnet, Dominique , Stradella, Agostina , Tischkowitz, Marc D. , Tognazzo, Silvia , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Luijt, Rob B. van der , Yannoukakos, Drakoulis , Neuhausen, Susan L. , Rebbeck, Timothy R.
Cancer Research | November 13, 2019 | Volume: 80 | Issue: 3 | Pages: 624-638
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12–11.54; P = 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
Friebel, Tara M. , Friedman, Eitan , Hamann, Ute, Huo, Dezheng , Kwong, Ava , Oláh, Edith , Olopade, Olufunmilayo I., Solano, Ángela R. , Teo, Soo‐Hwang , Thomassen, Mads , Weitzel, Jeffrey N. , Chan, TL, Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inêz , Park, Sue K. , Torres, Diana , Rensburg, Elizabeth J. van , McGuffog, Lesley, Aalfs, Cora M. , Abugattas, Julio E. , Aittomäki, Kristiina, Andrews, Lesley , Andrulis, Irene L., Arason, Aðalgeir , Arun, Banu, Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo , Balmañà, Judith , Barile, Monica, Barkardóttir, Rósa B. , Barrowdale, Daniel , Benı́tez, Javier , Berger, Andreas, Berger, Raanan , Blanco, Amie , Blazer, Kathleen R. , Blok, Marinus J. , Bonadona, Valérie , Bradbury, Angela R. , Brewer, Carole, Buecher, Bruno , Caldés, Trinidad, Caliebe, Almuth , Caligo, Maria A. , Caputo, Sandrine M. , Chiquette, Jocelyne , Claes, Kathleen , Collée, J. Margriet, Davidson, Rosemarie, Hoya, Miguel de la , Leeneer, Kim De , Pauw, Antoine De , Delnatte, Capucine, Ding, Yuan Chun , Ditsch, Nina , Dorfling, Cecilia M., Dworniczak, Bernd , Eason, Jacqueline , Easton, Douglas F. , Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , EMBRACE, Engel, Christoph , Engert, Stefanie, Evans, D. Gareth , Faivre, Laurence, Feliubadaló, Lídia , Ferrer, Sandra Fert, Foretová, Lenka , Fowler, Jeffrey M., Frost, Debra, Galvão, Henrique C.R. , Ganz, Patricia A. , Gauthier‐Villars, Marion , Gehrig, Andrea, Collaborators, GEMO Study, Gerdes, Anne‐Marie , Gesta, Paul , Giannini, Giuseppe , Giraud, Sophie , Glendon, Gord , Godwin, Andrew K., Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hauke, Jan , HEBON, Henderson, Alex, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Izatt, Louise , Izquierdo, Á. , Jakubowska, Anna , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Vijai, Joseph , Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Investigators, kConFab, Kim, Sung-Won, Konstantopoulou, Irene , Korach, Jacob, Laitman, Yael , Lasset, Christine, Lázaro, Conxi , Lee, Annette, Lee, Min Hyuk , Lester, Jenny, Lesueur, Fabienne , Liljegren, Annelie, Lindor, Noralane M. , Longy, Michel, Loud, Jennifer T. , Lu, Karen H. , Lubiński, Jan , Macháčková, Eva , Manoukian, Siranoush , Mari, Véronique , Martínez-Bouzas, Cristina, Mátrai, Zoltán , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Mickys, Ugnius, Montagna, Marco , Moysich, Kirsten B., Mulligan, Anna Marie , Musinsky, Jacob, Ngeow, Joanne , Niederacher, Dieter , Nielsen, Henriette Roed, Nielsen, Finn C., Offit, Kenneth, Öfverholm, Anna , Ong, Kai‐Ren , Osório, Ana , Papp, J., Pasini, Barbara , Pedersen, Inge Søkilde , Peixoto, Ana , Peruga, Nina, Peterlongo, Paolo , Pohl, Esther, Pradhan, Nisha , Prajzendanc, Karolina , Prieur, Fabienne, Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rodriguez, Gustavo C. , Rogers, Mark T., Rudaitis, Vilius , Schmidt, Ane Yde , Schmutzler, Rita K., Senter, Leigha , Shah, Payal D. , Side, Lucy, Simard, Jacques , Skytte, Anne‐Bine , Slavin, Thomas P. , Snape, Katie , Sobol, Hagay, Southey, Melissa C. , Sukiennicki, Grzegorz, Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Terry, Mary Beth , Teulé, Àlex , Thomas, Abigail, Thull, Darcy L. , Tognazzo, Silvia , Toland, Amanda Ewart, Topka, Sabine , Trainer, Alison H. , Hout, Annemieke H. van der, Kolk, Lizet E. van der, Luijt, Rob B. van der , Heetvelde, Mattias Van , Varesco, Liliana, Varon‐Mateeva, Raymonda, Vega, Ana , Villarreal‐Garza, Cynthia , Wachenfeldt, Anna von , Walker, Lisa, Wang‐Gohrke, Shan , Wappenschmidt, Barbara, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K. , Selkirk, Christina G. , Hulick, Peter J. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Nathanson, Katherine L. , Durocher, Francine , Olopade, Olufunmilayo I. , Faivre, Laurence , Białkowska, Katarzyna , Caligo, Maria A , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Moysich, Kirsten , Vega, Ana , de la Hoya, Miguel , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Azzollini, Jacopo , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , Joseph, Vijai , Konstantopoulou, Irene , Olopade, Olufunmilayo I , Southey, Melissa C , van der Luijt, Rob B , Jakubowska, Anna , Palmero, Edenir I , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Izquierdo, Angel , Lazaro, Conxi , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Senter, Leigha , Topka, Sabine , Rebbeck, Timothy R. , Couch, Fergus J. , Parsons, Michael T. , Leslie, Goska , Adlard, Julian , Agata, Simona , Arnold, Norbert , Bonanni, Bernardo , Buys, Saundra S. , Campbell, Ian , Chung, Wendy K. , Cook, Jackie A , Dı́ez, Orland , Domchek, Susan M. , Velázquez, Carolina , EMBRACE, Garber, Judy E. , Collaborators, GEMO Study, Gronwald, Jacek , HEBON, Hentschel, Julia , Hogervorst, Frans B.L., Isaacs, Claudine , John, Esther M. , Karlan, Beth Y. , Lasa, Adriana , Lasset, Christine , Liljegren, Annelie , Meindl, Alfons , Miller, Austin , Moysich, Kirsten B. , Neuhausen, Susan L. , Nevanlinna, Heli , Nguyen, Huu Phuc , Nussbaum, Robert L. , Papi, Laura , Pujol, Pascal , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Singer, Christian F. , Sobol, Hagay , Steele, Linda Roslyn , Steinemann, Doris , Szabo, Csilla I. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Wappenschmidt, Barbara , Weber, Bernhard H. F. , Yannoukakos, Drakoulis , Spurdle, Amanda B. , Faivre, Laurence , Rashid, Muhammad U , De Leeneer, Kim , Feliubadaló, Lidia , Hauke, Jan , Pasini, Barbara , Ngeow, Joanne , Manoukian, Siranoush , Lubinski, Jan , Terry, Mary Beth , Villarreal-Garza, Cynthia , Balmaña, Judith , Kwong, Ava
Human Mutation | February 15, 2018 | Volume: 39 | Issue: 5 | Pages: 593-620
BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
Mesman, Romy L.S. , Nicolai, Catharina Von , Ehlén, Åsa , Guidugli, Lucia, Martin, Charlotte , Calléja, Fabienne M.G.R., Hallberg, Emily, Hinton, Jamie, Lilyquist, Jenna , Hu, Chunling , Aalfs, Cora M. , Aittomäki, Kristiina, Andrulis, Irene L. , Beckmann, Matthias W. , Benı́tez, Javier , Bogdanova, Natalia , Bojesen, Stig E. , Bolla, Manjeet K. , Børresen‐Dale, Anne‐Lise , Brauch, Hiltrud , Brennan, Paul , Brenner, Hermann , Brouwers, Barbara , Brüning, Thomas , Burwinkel, Barbara , Chang‐Claude, Jenny , Chenevix‐Trench, Georgia , Cheng, Ching‐Yu , Choi, Ji‐Yeob , Collée, J. Margriet, Darabi, Hatef, Dörk, Thilo , Fasching, Peter A. , Figueroa, Jonine D. , Flyger, Henrik, García‐Closas, Montserrat , Glendon, Gord, Guénel, Pascal , Haiman, Christopher A., Hamann, Ute, Hartman, Mikael , Hogervorst, Frans B.L., Hopper, John L. , Jakubowska, Anna , Kang, Daehee , Kosma, Veli‐Matti , Kristensen, Vessela N. , Lai, Kah-Nyin, Lambrechts, Diether , Li, Jingmei , Lindblom, Annika , Lubiński, Jan , Macháčková, Eva , Mannermaa, Arto, Margolin, Sara , Matsuo, Keitaro , Miao, Hui , Michailidou, Kyriaki , Muir, Kenneth , Olswold, Curtis, Oosterwijk, Jan J.C., Osório, Ana , Peterlongo, Paolo , Peto, Julian , Pylkäs, Katri , Radice, Paolo , Rashid, Muhammad Usman , Rhenius, Valerie , Sangrajrang, Suleeporn , Sawyer, Elinor J. , Schmidt, Marjanka K. , Schoemaker, Minouk J. , Seynaeve, Caroline, Shah, Mitul , Shrubsole, Martha J. , Slager, Susan, Southey, Melissa C. , Swerdlow, Anthony J. , Teo, Soo‐Hwang , Tomlinson, Ian , Torres, Diana , Truong, Thérèse , Kolk, Lizet E. van der, Wang, Qin, Winqvist, Robert , Wu, Anna H. , Yu, Jyh‐Cherng , Zheng, Wei , Zheng, Ying , Leary, Jennifer, Walker, Logan C. , Foretová, Lenka , Claes, Kathleen , Varesco, Liliana , Moghadasi, Setareh , Easton, Douglas F. , Devilee, Peter , Vrieling, Harry , Monteiro, Álvaro N.A. , Goldgar, David E., Carreira, Aura , Vreeswijk, Maaike P.G. , Bowtell, David D.L. , Lambrechts, Diether , Shimelis, Hermela , Meeks, Huong , Anton‐Culver, Hoda , Arndt, Volker , Broeks, Annegien , Cox, Angela , Cross, Simon S. , Czene, Kamila , Dennis, Joe , dos‐Santos‐Silva, Isabel , Dunning, Alison M. , Giles, Graham G. , Hall, Per N , Hollestelle, Antoinette , Ito, Hidemi , Marchand, Loı̈c Le , Lophatananon, Artitaya , Mannermaa, Arto, Marmé, Frederik , Milne, Roger L. , Neuhausen, Susan L. , Nevanlinna, Heli , Olson, Janet E. , Pharoah, Paul D.P. , Rudolph, Anja , Shen, Chen‐Yang , Shu, Xiao‐Ou , Stram, Daniel O. , Asperen, Christi J. van , Wang, Qin, Fostira, Florentia , Spurdle, Amanda B. , Goldgar, David E., Couch, Fergus J. , Dörk, Thilo , Lambrechts, Diether , Peterlongo, Paolo , Teo, Soo H , Shrubsole, Martha J , Monteiro, Alvaro N , Swerdlow, Anthony J , Vreeswijk, Maaike P G , Radice, Paolo , Claes, Kathleen B M , Southey, Melissa C , Muir, Kenneth , Matsuo, Keitaro , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Guénel, Pascal , Hartman, Mikael , Li, Jingmei , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Hu, Chunling , Michailidou, Kyriaki , Bogdanova, Natalia V , Benitez, Javier , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Bowtell, David D , Pylkäs, Katri , Rashid, Muhammad U , Devilee, Peter , Lubinski, Jan , Bojesen, Stig E , Schoemaker, Minouk J , Truong, Therese , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Kang, Daehee
Cancer Research | March 10, 2017 | Volume: 77 | Issue: 11 | Pages: 2789-2799
Abstract Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case–control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789–99. ©2017 AACR.
Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21
Hamdi, Yosr , Collaborators, NBCS, Soucy, Penny, Adoue, Véronique , Michailidou, Kyriaki , Canisius, Sander , Lemaçon, Audrey , Droit, Arnaud , Andrulis, Irene L. , Baynes, Caroline, Blomqvist, Carl , Bogdanova, Natalia , Bojesen, Stig E. , Bolla, Manjeet K. , Børresen‐Dale, Anne‐Lise , Brand, Judith S. , Brauch, Hiltrud , Brenner, Hermann , Burwinkel, Barbara , Chang‐Claude, Jenny , Darabi, Hatef, Devilee, Peter , Dörk, Thilo , Eriksson, Mikael , Fasching, Peter A. , Figueroa, Jonine D. , Flyger, Henrik, García‐Closas, Montserrat , Goldberg, Mark S. , González‐Neira, Anna , Grenaker-Alnæs, Grethe Irene, Guénel, Pascal , Haeberle, Lothar, Haiman, Christopher A., Hamann, Ute, Hallberg, Emily, Hooning, Maartje J. , Jakubowska, Anna , Jones, Michael E. , Kabisch, Maria, Kataja, Vesa , Lambrechts, Diether , Lindblom, Annika , Lubiński, Jan , Mannermaa, Arto, Maranian, Mel, Margolin, Sara , Marme, Frederik, Neven, Patrick , Olswold, Curtis, Peto, Julian, Plaseska‐Karanfilska, Dijana , Pylkäs, Katri , Radice, Paolo , Sawyer, Elinor J. , Schmidt, Marjanka K. , Shu, Xiao-Ou , Southey, Melissa C. , Swerdlow, Anthony J. , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Torres, Diana , Truong, Thérèse , Vachon, Celine M. , Ouweland, Ans M.W. van den, Wang, Qin , Winqvist, Robert , Investigators, kConFab AOCS, Benı́tez, Javier , Chenevix‐Trench, Georgia , Dunning, Alison M. , Kristensen, Vessela N. , Easton, Douglas F. , Pastinen, Tomi , Simard, Jacques , Durocher, Francine , Zheng, Wei , Thorne, Heather , Lambrechts, Diether , Vachon, Celine, Collaborators, NBCS, Anton‐Culver, Hoda , Arndt, Volker , Bonanni, Bernardo , Broeks, Annegien , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Dennis, Joe , dos‐Santos‐Silva, Isabel , Eriksson, Mikael , Giles, Graham G. , Hooning, Maartje J. , Hopper, John L. , Marchand, Loı̈c Le , Mannermaa, Arto , Milne, Roger L. , Neuhausen, Susan L. , Nevanlinna, Heli , Rudolph, Anja , Vachon, Celine M. , Zheng, Wei , Pharoah, Paul D.P. , Hall, Per N , Nord, Silje , Dörk, Thilo , Lambrechts, Diether , Swerdlow, Anthony J , Radice, Paolo , Southey, Melissa C , Dunning, Alison M , Jakubowska, Anna , Jones, Michael E , Lambrechts, Diether , Brenner, Hermann , Guénel, Pascal , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Michailidou, Kyriaki , Bogdanova, Natalia V , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Pylkäs, Katri , Devilee, Peter , Lubinski, Jan , Bojesen, Stig E , Truong, Therese , Brauch, Hiltrud , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Droit, Arnaud
Oncotarget | November 28, 2016 | Volume: 7 | Issue: 49 | Pages: 80140-80163
PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
Southey, Melissa C. , Goldgar, David E, Winqvist, Robert , Pylkäs, Katri , Michailidou, Kyriaki , Rensburg, Elizabeth J. van , Heikkinen, Tuomas , Hopper, John L. , Dörk, Thilo , Claes, Kathleen , Teo, Zhi L. , Radice, Paolo , Catucci, Irene, Peterlongo, Paolo , Odefrey, Fabrice, Dowty, James G., Schmidt, Marjanka K. , Hogervorst, Frans B.L., Verhoef, Senno, Carpenter, Jane, Clarke, Christine L. , Scott, Rodney J. , Fasching, Peter A. , Haeberle, Lothar, Ekici, Arif B. , Beckmann, Matthias W. , Peto, Julian , Fletcher, Olivia , Johnson, Nichola , Bolla, Manjeet K. , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Marmé, F., Burwinkel, Barbara , Guénel, Pascal , Truong, Thérèse , Sanchez, Marie, Bojesen, Stig E. , Nielsen, Sune F. , Flyger, Henrik, Benı́tez, Javier , Zamora, M. Pilar , Menéndez, Primitiva, Brenner, Hermann , Stegmaier, Christa, Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Muranen, Taru , Aittomäki, Kristiina, Blomqvist, Carl , Bogdanova, Natalia , Antonenkova, Natalia, Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wauters, Els , Smeets, Dominiek, Beuselinck, Benoit , Floris, Giuseppe , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Vachon, Celine M. , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Kristensen, Vessela, Alnæs, Grethe Grenaker, Zheng, Wei , Hunter, David J. , Lindström, Sara, Hankinson, Susan E. , Kraft, Peter , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Jukkola‐Vuorinen, Arja , Grip, Mervi, Kauppila, Saila , Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, García‐Closas, Montserrat , Figueroa, Jonine D. , Lissowska, Jolanta , Darabi, Hatef, Eriksson, Mikael , Eccles, Diana M, Tapper, William , Gerty, Sue, Hooning, Maartje J. , Collée, J. Margriet, Tilanus‐Linthorst, Madeleine M.A., Li, Jingmei , Brand, Judith S. , Humphreys, Keith , Reed, Malcolm , Luccarini, Craig , Baynes, Caroline, Dunning, Alison M. , Hamann, Ute, Torres, Diana , Ulmer, Hans Ulrich, Rüdiger, Thomas , Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Slager, Susan, Yannoukakos, Drakoulis , Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nick , Jones, Michael E. , González‐Neira, Anna , Pita, Guillermo , Alonso, M. Rosario, Álvarez, Núria, Herrero, Daniel, Tessier, Daniel C., Vincent, Daniel , Bacot, François, Simard, Jacques , Dumont, Martine , Soucy, Penny, Eeles, Rosalind A. , Muir, Kenneth , Grönberg, Henrik , Schleutker, Johanna , Nordestgaard, Børge G. , Weischer, Maren , Travis, Ruth C. , Neal, David E. , Donovan, Jenny , Hamdy, Freddie C. , Stanford, Janet L. , Blot, William J. , Thibodeau, Stephen N. , Schaid, Daniel J. , Kelley, Joseph L., Maier, Christiane, Kibel, Adam S. , Butterbach, Katja, Kaneva, Radka , Batra, Jyotsna , Teixeira, Manuel R. , Olama, Ali Amin Al , Benlloch, Sara, Hartmann, Arndt , Hein, Alexander , Ruebner, Matthias , Lambrechts, Diether , Nieuwenhuysen, Els Van , Vergote, Ignace , Lambretchs, Sandrina, Rossing, Mary Anne, Nickels, Stefan , Eilber, Ursula, Wang‐Gohrke, Shan , Odunsi, Kunle , Sucheston‐Campbell, Lara, Friel, Grace , Lurie, Galina, Killeen, Jeffrey , Goodman, Marc T. , Runnebaum, Ingo B., Hillemanns, Peter , Pelttari, Liisa M. , Edwards, Robert P., Ness, Roberta B., Moysich, Kirsten B., Heitz, Florian , Harter, Philipp , Kommoss, Stefan , Walsh, Christine , Lester, Jenny, Jensen, Allan , Høgdall, Estrid , Peissel, Bernard , Bernard, Loris, Goode, Ellen L. , Vierkant, Robert A. , Cunningham, Julie M. , Fogarty, Zachary C. , Kalli, Kimberly R., Liang, Dong , Lu, Karen H., Hildebrandt, Michelle A.T., Wu, Xifeng , Levine, Douglas A. , Bisogna, Maria, Iversen, Edwin S., Marks, Jeffrey R. , Akushevich, Lucy , Schildkraut, Joellen M. , Terry, Kathryn L. , Stampfer, Meir J. , Tworoger, Shelley S. , Olson, Sara H. , Salvesen, Helga B., Altena, Anne M. van , Aben, Katja K.H. , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Bean, Yukie T., Kelemen, Linda E., Le, Nhu D. , Górski, Bohdan , Menkiszak, Janusz , Høgdall, Claus , Lundvall, Lene, Nedergaard, Lotte , Engelholm, Svend Aage, Dicks, Ed , Campbell, Ian , McNeish, Iain A. , Whittemore, Alice S. , Rothstein, Joseph H. , McGuire, Valerie, Sieh, Weiva , Cai, Hui , Teten, Rachel Threet, Sutphen, Rebecca , McLaughlin, John R, Narod, Steven A., Phelan, Catherine M., Monteiro, Álvaro N.A. , Fenstermacher, David, Lin, Hui‐Yi , Sellers, Thomas A. , Chen, Y. Ann , Chen, Zhihua , Gayther, Simon A. , Ramus, Susan J. , Menon, Usha , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Moes-Sosnowska, Joanna , Kupryjańczyk, Jolanta , Song, Honglin , Winship, Ingrid , Chenevix‐Trench, Georgia , Tavtigian, Sean V. , Easton, Doug , Lu, Karen H. , Durocher, Francine , Eccles, Diana , Lambrechts, Diether , Vachon, Celine, Pankratz, Vernon S, Thibodeau, Stephen, Goldgar, David E, Couch, Fergus J. , Tischkowitz, Marc D. , Foulkes, William D. , Dennis, Joe , Nevanlinna, Heli , Reis‐Filho, Jorge S. , Tsimiklis, Helen , Broeks, Annegien , dos‐Santos‐Silva, Isabel , Yang, Rongxi , Ménégaux, F. , Sanchez, Marie, Pérez, José Ignacio Arias , Anton‐Culver, Hoda , Neuhausen, Susan L. , Ziogas, Argyrios , Clarke, Christina A. , Arndt, Volker , Mannermaa, Arto, Spurdle, Amanda B. , Group, Australian Ovarian Cancer Study, Rudolph, Anja , Seibold, Petra , Olson, Janet E. , Vachon, Celine M. , Pankratz, V. Shane , Marchand, Loı̈c Le , Kristensen, Vessela N. , Hankinson, Susan E. , Hollestelle, Antoinette , Chanock, Stephen Jacob , Czene, Kamila , Eriksson, Mikael , Eccles, Diana M, Rafiq, Sajjad , Hooning, Maartje J. , Martens, John W.M. , Hall, Per N , Cox, Angela , Toland, Amanda Ewart , Ambrosone, Christine B. , Wiklund, Fredrik E. , Khaw, Kay‐Tee , Cybulski, Cezary , Cannon‐Albright, Lisa , Park, Jong, Kote‐Jarai, Zsofia , Renner, Stefan P. , Doherty, Jennifer A. , Wilkens, Lynne R. , Bützow, Ralf C. , Modugno, Francesmary , Moysich, Kirsten B., Bois, Andreas du , Karlan, Beth Y. , Kjær, Susanne K. , Bonanni, Bernardo , Fridley, Brooke L. , Larson, Melissa C. , Hildebrandt, Michelle A.T. , Dao, Fanny , Berchuck, Andrew , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Orlow, Irene , Bjørge, Line , Pejovic, Tanja B. , Brooks‐Wilson, Angela , Cook, Linda S. , Gronwald, Jacek , Tyrer, Jonathan P. , Paul, James , Siddiqui, Nadeem , Glasspool, Rosalind , Shu, Xiao‐Ou , McLaughlin, John R, Permuth, Jennifer B. , Gentry‐Maharaj, Aleksandra , Berg, David Van Den , Pharoah, Paul D.P. , Giles, Graham G. , Milne, Roger L. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Tworoger, Shelley S , van Rensburg, Elizabeth J , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Radice, Paolo , Lissowska, Jolanta , Claes, Kathleen B M , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Menkiszak, Janusz , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Lin, Hui-Yi , Fogarty, Zachary C , Dunning, Alison M , Heitz, Florian , Jakubowska, Anna , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , Li, Jingmei , Muranen, Taru A , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Winship, Ingrid M , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Batra, Jyotsna , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Goodman, Marc T , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Journal of Medical Genetics | September 5, 2016 | Volume: 53 | Issue: 12 | Pages: 800-811
Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing
Easton, Douglas F. , Lesueur, Fabienne , Decker, Brennan , Michailidou, Kyriaki , Li, Jun , Allen, Jamie , Luccarini, Craig , Pooley, Karen A. , Shah, Mitul , Bolla, Manjeet K. , Wang, Qin, Ahmad, Jamil , Thompson, Ella R. , Pertesi, Maroulio , Voegele, Catherine , Mebirouk, Noura, Robinot, Nivonirina , Forey, Nathalie, Luben, Robert , Aittomäki, Kristiina, Group, Australian Ovarian Cancer Study, Baynes, Caroline, Beckman, Matthias W., Benı́tez, Javier , Blot, William J. , Bogdanova, Natalia , Bojesen, Stig E. , Brenner, Hermann , Chang‐Claude, Jenny , Chia, Kee Seng , Choi, Ji‐Yeob , Conroy, Don, Darabi, Hatef, Devilee, Peter , Eriksson, Mikael , Fasching, Peter A. , Figueroa, Jonine D. , Flyger, Henrik, García‐Closas, Montserrat , Giles, Graham G. , Glendon, Gord, Guénel, Pascal , Haiman, Christopher A., Hart, Steven N. , Hartman, Mikael , Hooning, Maartje J. , Hsiung, Chia‐Ni , Jakubowska, Anna , James, Paul A. , John, Esther M. , Johnson, Nichola , Jones, Michael E. , Kabisch, Maria, Kang, Daehee , Investigators, kConFab, Kosma, Veli‐Matti , Kristensen, Vessela, Lambrechts, Diether , Li, Na , Investigators, Lifepool, Lindblom, Annika , Long, Jirong , Lophatananon, Artitaya, Lubiński, Jan , Mannermaa, Arto, Manoukian, Siranoush , Margolin, Sara , Matsuo, Keitaro , Meindl, Alfons , Mitchell, Gillian, Investigators, NBCS, Nevelsteen, Ines, Ouweland, Ans van den, Peterlongo, Paolo , Phuah, Sze Yee, Pylkäs, Katri , Rowley, Simone M. , Sangrajrang, Suleeporn , Schmutzler, Rita K., Shen, Chen‐Yang , Southey, Melissa C. , Surowy, Harald , Swerdlow, Anthony J. , Teo, Soo‐Hwang , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Torres, Diana , Truong, Thérèse , Vachon, Celine M. , Verhoef, Senno, Wong‐Brown, Michelle W. , Zheng, Wei , Zheng, Ying , Scott, Rodney J. , Andrulis, Irene L. , Wu, Anna H. , Hopper, John L. , Winqvist, Robert , Burwinkel, Barbara , Sawyer, Elinor J. , Schmidt, Marjanka K. , Dörk, Thilo , Brauch, Hiltrud , Hamann, Ute, Fletcher, Olivia , Campbell, Ian , Dunning, Alison M. , Calvez‐Kelm, Florence Le , Goldgar, David E, Tavtigian, Sean V. , Chenevix‐Trench, Georgia , Thorne, Heather , Lambrechts, Diether , Luben, Robert N , Vachon, Celine, Decker, Brennan , Wang, Qin, Dennis, Joe , Damiola, Francesca , Durand, Geoffroy , Ahmed, Shahana , Anton‐Culver, Hoda , Arndt, Volker , Group, Australian Ovarian Cancer Study, Berg, David Van Den , Cox, Angela , Cross, Simon S. , Czene, Kamila , Eriksson, Mikael , Fostira, Florentia , González‐Neira, Anna , Hall, Per N , Hooning, Maartje J. , Ito, Hidemi , Investigators, kConFab, Kristensen, Vessela N. , Investigators, Lifepool, Mannermaa, Arto, Meindl, Alfons , Muir, Kenneth , Investigators, NBCS, Shu, Xiao‐Ou , Vachon, Celine M. , Nevanlinna, Heli , Couch, Fergus J. , Rudolph, Anja , Neuhausen, Susan L. , Milne, Roger L. , Pharoah, Paul D.P. , Goldgar, David E, Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Teo, Soo H , Swerdlow, Anthony J , Campbell, Ian G , John, Esther M , Southey, Melissa C , Matsuo, Keitaro , Hart, Steven N , Dunning, Alison M , Jakubowska, Anna , Jones, Michael E , Lambrechts, Diether , Brenner, Hermann , Guénel, Pascal , Hartman, Mikael , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Michailidou, Kyriaki , Bogdanova, Natalia V , Benitez, Javier , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Pylkäs, Katri , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Truong, Therese , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Kang, Daehee
Journal of Medical Genetics | April 22, 2016 | Volume: 53 | Issue: 5 | Pages: 298-309
Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.
Fine‐scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer
Shi, Jiajun , Zhang, Yanfeng , Zheng, Wei , Michailidou, Kyriaki , Ghoussaini, Maya , Bolla, Manjeet K. , Wang, Qin, Beesley, Jonathan, Kar, Siddhartha , Andrulis, Irene L. , Beckmann, Matthias W. , Zhao, Zhiguo , Benı́tez, Javier , Beeghly‐Fadiel, Alicia, Blot, William J. , Bogdanova, Natalia , Bojesen, Stig E. , Brauch, Hiltrud , Brenner, Hermann , Brinton, Louise A. , Brüning, Thomas , Burwinkel, Barbara , Cai, Hui , Canisius, Sander , Chang‐Claude, Jenny , Choi, Ji‐Yeob , Couch, Fergus J. , Darabi, Hatef, Devilee, Peter , Droit, Arnaud , Dörk, Thilo , Fasching, Peter A. , Fletcher, Olivia , Flyger, Henrik, Fostira, Florentia, Gaborieau, Valérie , García‐Closas, Montserrat , Giles, Graham G. , Grip, Mervi, Guénel, Pascal , Haiman, Christopher A., Hamann, Ute, Hartman, Mikael , Miao, Hui , Hopper, John L. , Hsiung, Chia‐Ni , Investigators, kConFab, Jakubowska, Anna , Johnson, Nichola , Torres, Diana , Kabisch, Maria, Kang, Daehee , Khan, Sofia , Knight, Julia A. , Kosma, Veli‐Matti, Lambrechts, Diether , Li, Jingmei , Lindblom, Annika , Lubiński, Jan , Mannermaa, Arto, Manoukian, Siranoush , Margolin, Sara , Matsuo, Keitaro , McLean, Catriona , Meindl, Alfons, Børresen‐Dale, Anne‐Lise , Orr, Nick , Ouweland, Ans M.W. van den, Peterlongo, Paolo , Putti, Thomas Choudary , Sangrajrang, Suleeporn , Sawyer, Elinor J. , Schmidt, Marjanka K. , Schmutzler, Rita K., Shen, Chen‐Yang , Hou, Ming‐Feng , Shrubsole, Matha J., Southey, Melissa C. , Swerdlow, Anthony J. , Teo, Soo‐Hwang , Thienpont, Bernard , Tollenaar, Robert A.E.M., Tomlinson, Ian , Truong, Thérèse , Tseng, Chiu-Chen , Wen, Wanqing , Winqvist, Robert , Wu, Anna H. , Yip, Cheng Har , Zheng, Ying , Floris, Giuseppe , Cheng, Ching‐Yu , Hooning, Maartje J. , Seynaeve, Caroline, Kristensen, Vessela N., Simard, Jacques , Chenevix‐Trench, Georgia , Dunning, Alison M. , Antoniou, Antonis C. , Easton, Douglas F. , Long, Jirong , Durocher, Francine , Thorne, Heather , Shrubsole, Martha J. , Lambrechts, Diether , Wang, Qin, Dennis, Joe , Lush, Michael J. , Milne, Roger L. , Shu, Xiao‐Ou , Anton‐Culver, Hoda , Arndt, Volker , Guo, Xingyi , Beeghly‐Fadiel, Alicia , Broeks, Annegien , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Hollestelle, Antoinette , Investigators, kConFab, Ito, Hidemi , Lophatananon, Artitaya , Mannermaa, Arto , Marchand, Loı̈c Le , Marmé, Frederik , Meindl, Alfons, Muir, Kenneth , Neuhausen, Susan L. , Nevanlinna, Heli , Nord, Silje , Olson, Janet E. , Rudolph, Anja , Toland, Amanda Ewart , Zamora, Pilar M. , Hooning, Maartje J. , Martens, John W.M. , Kristensen, Vessela N. , Hall, Per N , Pharoah, Paul D.P. , Cai, Qiuyin , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Teo, Soo H , Shrubsole, Martha J , Swerdlow, Anthony J , Southey, Melissa C , Matsuo, Keitaro , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Guénel, Pascal , Hartman, Mikael , Li, Jingmei , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Michailidou, Kyriaki , Bogdanova, Natalia V , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Kar, Siddhartha , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , Kang, Daehee , Droit, Arnaud
International Journal of Cancer | April 18, 2016 | Volume: 139 | Issue: 6 | Pages: 1303-1317
Previous genome‐wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine‐mapping study across 2.06 Mb (chr8:127,561,724–129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93–0.97, conditional p = 5.8 × 10−6), rs7815245 (OR = 0.94, 95% CI = 0.91–0.96, conditional p = 1.1 × 10−6) and rs2033101 (OR = 1.05, 95% CI = 1.02–1.07, conditional p = 1.1 × 10−4) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r2 = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.