Rosenberg, Efraim H.
https://orcid.org/0000-0002-3859-6941
Mayo Clinic
The Netherlands Cancer Institute
Citations 2
A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2
Zanti, Maria , O'Mahony, Denise G , Li, Hongyan , Aittomäkkiki, Kristiina, Andrulis, Irene L. , Aronson, Kristan J. , Bolla, Manjeet K. , Brenner, Hermann , Caputo, Sandrine M. , Chang‐Claude, Jenny , Collaborators, GC-HBOC study, Daly, Mary B., Nicolo, Arcangela De , Eccles, Diana M., Engel, Christoph , Evans, D. Gareth , Fasching, Peter A. , Giele, Willemina R. R. Geurts -, Glendon, Gord , Goldberg, Mark S. , Gómez, E. , Güendert, Melanie, Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harkness, Elaine F. , Hogervorst, Frans B.L., Hoppe, Reiner , Houdayer, Claude , Houlston, Richard S. , Howell, Anthony , Investigators, ABCTB, Jakimovska, Milena , John, Esther M. , Kristensen, Vessela N. , Lambrechts, Diether , Léone, Mélanie, Lindblom, Annika , Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush , Menon, Usha , Offit, Kenneth, Park, Sue K. , Peto, Julian , Plaseska‐Karanfilska, Dijana , Romero, Atocha , Schmutzler, Rita K. , Stone, Jennifer , Tapper, William , Teo, Soo‐Hwang , Thomassen, Mads , Vachon, Celine M. , Vega, Ana , Wang, Qin , Wappenschmidt, Barbara , Zheng, Wei , Easton, Douglas F. , Goldgar, David E., Eccles, Diana , Lambrechts, Diether , Houdayer, Claude , Lambrechts, Diether , Teo, Soo H , Eccles, Diana , Menon, Usha , Houlston, Richard S , Vega, Ana , Evans, D Gareth , John, Esther M , Lambrechts, Diether , Brenner, Hermann , Romero, Atocha , Engel, Christoph , Zheng, Wei , Stone, Jennifer , Gómez-García, Encarna B , De Nicolo, Arcangela , Manoukian, Siranoush , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Parsons, Michael T. , Dennis, Joe , Anton‐Culver, Hoda , Augustinsson, Annelie , Becher, Heiko , Bojesen, Stig E. , Brown, Melissa A. , Buys, Saundra S. , Canzian, Federico , Castelao, Jose E. , Czene, Kamila , Devilee, Peter , Dörk, Thilo , Dunning, Alison M. , Dwek, Miriam , Gago-Domínguez, Manuela , García‐Closas, Montserrat , García-Sáenz, José Á. , Gentry‐Maharaj, Aleksandra , Geurts-Giele, Willemina R.R. , Giles, Graham G. , Guénel, Pascal , Hall, Per N , Hollestelle, Antoinette , Hopper, John L. , Jakubowska, Anna , Jernström, Helena , Kaaks, Rudolf , Kitahara, Cari M. , Koutros, Stella , Kraft, Peter , Lacey, James V. , Léoné, Mélanie, Lubiński, Jan , Lush, Michael J. , Mannermaa, Arto, Margolin, Sara , Martı́nez, Marı́a Elena , Milne, Roger L. , Monteiro, Álvaro N.A. , Murphy, Rachel A. , Neuhausen, Susan L. , Nevanlinna, Heli , Newman, William G. , James, Paul A. , Peterlongo, Paolo , Punie, Kevin , Radice, Paolo , Rashid, Muhammad Usman , Rennert, Gad , Rosenberg, Efraim H. , Saloustros, Emmanouil , Sandler, Dale P. , Schmidt, Marjanka K. , Shu, Xiao‐Ou , Simard, Jacques , Southey, Melissa C. , Stoppa‐Lyonnet, Dominique , Tamimi, Rulla M. , Taylor, Jack A. , Teras, Lauren R. , Terry, Mary Beth , Troester, Melissa A. , Vachon, Celine M. , Vreeswijk, Maaike P.G. , Weinberg, Clarice R. , Wolk, Alicja , Feng, Bing , Couch, Fergus J. , Spurdle, Amanda B. , Michailidou, Kyriaki
Human Mutation | September 15, 2023 | Volume: 2023 | Issue: No issue available | Pages: 1-17
A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity—findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
19p13.1 Is a Triple-Negative–Specific Breast Cancer Susceptibility Locus
Stevens, Kristen N., Fredericksen, Zachary, Vachon, Celine M. , Margolin, Sara , Lindblom, Annika , Nevanlinna, Heli , Greco, Dario , Aittomäki, Kristiina, Blomqvist, Carl , Chang‐Claude, Jenny , Vrieling, Alina , Flesch‐Janys, Dieter, Sinn, Hans‐Peter , Wang‐Gohrke, Shan , Nickels, Stefan , Brauch, Hiltrud , Ko, Yon‐Dschun, Fischer, Hans‐Peter , Schmutzler, Rita K., Meindl, Alfons, Bartram, Claus R., Schott, Sarah , Engel, Christoph , Weaver, JoEllen , Sharma, Priyanka , Brenner, Hermann , Stegmaier, Christa, Miron, Penelope , Yannoukakos, Drakoulis , Stavropoulou, Alexandra , Fountzilas, George , Swann, Ruth , Dwek, Miriam , Perkins, Annie, Zamora, María Pilar, Bojesen, Stig E. , Nielsen, Sune F. , Nordestgaard, Børge G. , Flyger, Henrik, Guénel, Pascal , Truong, Thérèse , Ménégaux, F. , Cordina‐Duverger, Emilie, Burwinkel, Barbara , Marmé, Frederick, Schneeweiß, Andreas , Sohn, Christof , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Peto, Julian , Johnson, Nichola , dos‐Santos‐Silva, Isabel , Fasching, Peter A. , Beckmann, Matthias W. , Hartmann, Arndt , Ekici, Arif B. , Lophatananon, Artitaya, Muir, Kenneth , Puttawibul, Puttisak, Wiangnon, Surapon , Schmidt, Marjanka K. , Braaf, Linde M., Rosenberg, Efraim H. , Hopper, John L. , Apicella, Carmel, Park, Daniel J. , Southey, Melissa C. , Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nicholas, Schoemaker, Minouk J. , Dur, Christina Clarke, Shen, Chen‐Yang , Yu, Jyh-Cherng, Hsu, Huan-Ming, Hsiung, Chia‐Ni , Hamann, Ute , Dünnebier, Thomas, Rüdiger, Thomas , Ulmer, Hans Ulrich, Dunning, Alison M. , Humphreys, Manjeet K., Wang, Qin , Cox, Angela , Cross, Simon S. , Reed, Malcolm , Czene, Kamila , Ademuyiwa, Foluso O. , Hwang, Helena, Eccles, Diana M., García‐Closas, Montserrat , Figueroa, Jonine D. , Sherman, Mark E., Lissowska, Jolanta , Seynaeve, Caroline, Tollenaar, Rob A.�E.�M. , Hooning, Maartje J. , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Grip, Mervi, John, Esther M. , Miron, Alexander, Alnæs, Grethe Grenaker, Kristensen, Vessela, Børresen‐Dale, Anne‐Lise , Giles, Graham G. , Baglietto, Laura , McLean, Catriona , Severi, Gianluca , Kosel, Matthew L., Pankratz, V.S., Slager, Susan, Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Barile, Monica, Lambrechts, Diether , Hatse, Sigrid , Dieudonné, Anne-Sophie, Christiaens, Marie-Rose, Chenevix‐Trench, Georgia , Chen, Xiaoqing, Mannermaa, Arto, Kosma, Veli‐Matti , Hartikainen, Jaana M. , Soini, Ylermi, Easton, Douglas F., Eccles, Diana , Orr, Nick , Thorne, Heather , Purrington, Kristen S. , Lambrechts, Diether , Vachon, Celine M. , Wang, Xianshu , Meindl, Alfons, Godwin, Andrew K. , Pathak, Harsh B. , Müller, Heiko , Arndt, Volker , Gogas, Helen J , Milne, Roger L. , Benı́tez, Javier , Pérez, José Ignacio Arias , Fletcher, Olivia , Broeks, Annegien , Orr, Nicholas, Anton‐Culver, Hoda , Ziogas, Argyrios , Bernstein, Leslie , Pharoah, Paul D.P. , Hall, Per N , Ambrosone, Christine B. , Eccles, Diana M., Devilee, Peter , Kristensen, Vessela N. , Kosel, Matthew , Olson, Janet E. , Beesley, Jonathan , Chen, Xiaoqing, Mannermaa, Arto, Couch, Fergus J. , Nevanlinna, H , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Eccles, Diana , Swerdlow, Anthony J , Radice, Paolo , Lissowska, Jolanta , John, Esther M , Southey, Melissa C , Sinn, Peter , Muir, Kenneth , Dunning, Alison M , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Hartikainen, Jaana M , Engel, Christoph , Chenevix-Trench, Georgia , Figueroa, Jonine D , Czene, Kamila , Ademuyiwa, Foluso O , Pylkäs, Katri , Yannoukakos, Drakoulis , Manoukian, Siranoush , Baglietto, Laura , Bojesen, Stig E , Purrington, Kristen S , Sharma, Priyanka , Schoemaker, Minouk J , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Cancer Research | February 13, 2012 | Volume: 72 | Issue: 7 | Pages: 1795-1803
Abstract The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.