Author: "Hart, Steven" / Publisher: german canc res ctr, div canc epidemiol, heidelberg, germany. - Searchworks@Jio Institute Digital Library Search Results

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1. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P<10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers., Correction in: Nature Communications, 2021. Vol. 12, no 1, article id 2986DOI: 10.1038/s41467-021-23162-4
Published: 2021
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2. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, Schmidt, Marjanka K., Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, and Schmidt, Marjanka K.
Abstract: Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast
Published: 2021
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3. Breast Cancer Risk Factors and Survival by Tumor Subtype : Pooled Analyses from the Breast Cancer Association Consortium

Author: Morra, Anna, Jung, Audrey Y., Behrens, Sabine, Keeman, Renske, Ahearn, Thomas U., Anton-Culver, Hoda, Arndt, Volker, Augustinsson, Annelie, Auvinen, Paivi K., Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Camp, Nicola J., Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Choi, Ji-Yeob, Clarke, Christine L., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Easton, Douglas F., Eccles, Diana M., Egan, Kathleen M., Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny N., Hart, Steven N., Hartman, Mikael, Heyworth, Jane S., Hoppe, Reiner, Hopper, John L., Hunter, David J., Ito, Hidemi, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Mavroudis, Dimitrios, Milne, Roger L., Muranen, Taru A., Newman, William G., Noh, Dong-Young, Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olsson, Hakan, Park-Simon, Tjoung-Won, Petridis, Christos, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J., Schneeweiss, Andreas, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Southey, Melissa C., Stram, Daniel O., Tamimi, Rulla M., Tapper, William, Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Wang, Sophia S., Williams, Justin A., Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yoo, Keun-Young, Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Yang, Xiaohong R., Eliassen, A. Heather, Holmes, Michelle D., Garcia-Closas, Montserrat, Teo, Soo Hwang, Schmidt, Marjanka K., Chang-Claude, Jenny, Morra, Anna, Jung, Audrey Y., Behrens, Sabine, Keeman, Renske, Ahearn, Thomas U., Anton-Culver, Hoda, Arndt, Volker, Augustinsson, Annelie, Auvinen, Paivi K., Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Camp, Nicola J., Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Choi, Ji-Yeob, Clarke, Christine L., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Easton, Douglas F., Eccles, Diana M., Egan, Kathleen M., Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny N., Hart, Steven N., Hartman, Mikael, Heyworth, Jane S., Hoppe, Reiner, Hopper, John L., Hunter, David J., Ito, Hidemi, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Mavroudis, Dimitrios, Milne, Roger L., Muranen, Taru A., Newman, William G., Noh, Dong-Young, Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olsson, Hakan, Park-Simon, Tjoung-Won, Petridis, Christos, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J., Schneeweiss, Andreas, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Southey, Melissa C., Stram, Daniel O., Tamimi, Rulla M., Tapper, William, Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Wang, Sophia S., Williams, Justin A., Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yoo, Keun-Young, Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Yang, Xiaohong R., Eliassen, A. Heather, Holmes, Michelle D., Garcia-Closas, Montserrat, Teo, Soo Hwang, Schmidt, Marjanka K., and Chang-Claude, Jenny
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 (P-adj > 0.30). The strongest associations were between all-cause mortality and BMI >= 30 versus 18.5-25 kg/m(2) [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.
Published: 2021
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4. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, Fletcher, Olivia, Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, and Fletcher, Olivia
Abstract: Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10(-18)); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10(-8)). Conclusions The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
Published: 2021
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5. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, Schmidt, Marjanka K., Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, and Schmidt, Marjanka K.
Abstract: Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast
Published: 2021
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6. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, Fletcher, Olivia, Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, and Fletcher, Olivia
Abstract: Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10(-18)); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10(-8)). Conclusions The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
Published: 2021
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7. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, Schmidt, Marjanka K., Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, and Schmidt, Marjanka K.
Abstract: Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast
Published: 2021
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8. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, Fletcher, Olivia, Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, and Fletcher, Olivia
Abstract: Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10(-18)); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10(-8)). Conclusions The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
Published: 2021
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9. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P<10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers., Correction in: Nature Communications, 2021. Vol. 12, no 1, article id 2986DOI: 10.1038/s41467-021-23162-4
Published: 2021
Full Text: View/download PDF

10. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P<10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers., Correction in: Nature Communications, 2021. Vol. 12, no 1, article id 2986DOI: 10.1038/s41467-021-23162-4
Published: 2021
Full Text: View/download PDF

11. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P<10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers., Correction in: Nature Communications, 2021. Vol. 12, no 1, article id 2986DOI: 10.1038/s41467-021-23162-4
Published: 2021
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12. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, Schmidt, Marjanka K., Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, and Schmidt, Marjanka K.
Abstract: Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast
Published: 2021
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13. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P<10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers., Correction in: Nature Communications, 2021. Vol. 12, no 1, article id 2986DOI: 10.1038/s41467-021-23162-4
Published: 2021
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14. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, Fletcher, Olivia, Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, and Fletcher, Olivia
Abstract: Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10(-18)); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10(-8)). Conclusions The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
Published: 2021
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15. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, Fletcher, Olivia, Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E., Schoemaker, Minouk J., Gilham, Clare, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Doerk, Thilo, Eliassen, A. Heather, Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., Hooning, Maartje J., Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Orban, Ester, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkas, Katri, Rennert, Gad, Rennert, Hedy S., Ruddy, Kathryn J., Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Scott, Christopher, Shu, Xiao-Ou, Simard, Jacques, Smichkoska, Snezhana, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tamimi, Rulla M., Taylor, Jack A., Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Wang, Sophia S., Weinberg, Clarice R., Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Howie, A. Forbes, Peto, Julian, dos-Santos-Silva, Isabel, Swerdlow, Anthony J., Chang-Claude, Jenny, Schmidt, Marjanka K., Orr, Nick, and Fletcher, Olivia
Abstract: Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10(-18)); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10(-8)). Conclusions The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
Published: 2021
Full Text: View/download PDF

16. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, Schmidt, Marjanka K., Morra, Anna, Escala-Garcia, Maria, Beesley, Jonathan, Keeman, Renske, Canisius, Sander, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Augustinsson, Annelie, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Bruening, Thomas, Buys, Saundra S., Caan, Bette, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Ting-Yuan David, Clarke, Christine L., Colonna, Sarah, V, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Dennis, Joe, Dork, Thilo, Dossus, Laure, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Garcia-Saenz, Jose A., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Guendert, Melanie, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N., Hartikainen, Jaana M., Hartmann, Arndt, He, Wei, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Howell, Anthony, Hunter, David J., Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey Y., Kaaks, Rudolf, Keupers, Machteld, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Linet, Martha, Luben, Robert N., Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martens, John W. M., Martinez, Maria Elena, Mavroudis, Dimitrios, Michailidou, Kyriaki, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nielsen, Sune F., Nordestgaard, Borge G., Olshan, Andrew F., Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peissel, Bernard, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Rack, Brigitte, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Lubinski, Jan, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Smichkoska, Snezhana, Southey, Melissa C., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Teras, Lauren R., Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Hurson, Amber N., Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Brauch, Hiltrud, Garcia-Closas, Montserrat, Pharoah, Paul D. P., Easton, Douglas F., Chenevix-Trench, Georgia, and Schmidt, Marjanka K.
Abstract: Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast
Published: 2021
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17. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P<10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers., Correction in: Nature Communications, 2021. Vol. 12, no 1, article id 2986DOI: 10.1038/s41467-021-23162-4
Published: 2021
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18. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Author: Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., Hollestelle, Antoinette, Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., and Hollestelle, Antoinette
Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Published: 2020
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19. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Author: Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., Hollestelle, Antoinette, Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., and Hollestelle, Antoinette
Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Published: 2020
Full Text: View/download PDF

20. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Author: Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., Hollestelle, Antoinette, Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., and Hollestelle, Antoinette
Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Published: 2020
Full Text: View/download PDF

21. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Author: Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., Hollestelle, Antoinette, Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., and Hollestelle, Antoinette
Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Published: 2020
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22. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Author: Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., Hollestelle, Antoinette, Liu, Jingjing, van der Smissen, Wendy J. C. Prager, Collee, J. Margriet, Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U., Aittomaki, Kristiina, Ambrosone, Christine B., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Augustinsson, Annelie, Auvinen, Paivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia, V, Bogdanova-Markov, Nadja, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L., Couch, Fergus J., Czene, Kamila, Daly, Mary B., Devilee, Peter, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Harrington, Patricia A., Hart, Steven N., Hartman, Mikael, Hillemanns, Peter, Hopper, John L., Hou, Ming-Feng, Hunter, David J., Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N., Kurian, Allison W., Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N., Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muir, Kenneth, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Offit, Kenneth, Olopade, Olufunmilayo, I, Olson, Janet E., Olsson, Hakan, Orr, Nick, Park, Sue K., Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rack, Brigitte, Rau-Murthy, Rohini, Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Ruebner, Matthias, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Simard, Jacques, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Tamimi, Rulla M., Tapper, William J., Teo, Soo H., Terry, Mary Beth, Torres, Diana, Truong, Therese, Untch, Michael, Vachon, Celine M., van Asperen, Christi J., Wolk, Alicja, Yamaji, Taiki, Zheng, Wei, Ziogas, Argyrios, Ziv, Elad, Torres-Mejia, Gabriela, Doerk, Thilo, Swerdlow, Anthony J., Hamann, Ute, Schmidt, Marjanka K., Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Hooning, Maartje J., Martens, John W. M., and Hollestelle, Antoinette
Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Published: 2020
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23. Genome-wide association study of germline variants and breast cancer-specific mortality

Author: Escala-Garcia, Maria, Guo, Qi, Doerk, Thilo, Canisius, Sander, Keeman, Renske, Dennis, Joe, Beesley, Jonathan, Lecarpentier, Julie, Bolla, Manjeet K., Wang, Qin, Abraham, Jean, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Boeckx, Bram, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brentnall, Adam, Brinton, Louise, Broberg, Per, Brock, Ian W., Brucker, Sara Y., Burwinkel, Barbara, Caldas, Carlos, Caldes, Trinidad, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Chin, Suet-Feung, Clarke, Christine L., Cordina-Duverger, Emilie, Couch, Fergus J., Cox, David G., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dunn, Janet A., Dunning, Alison M., Durcan, Lorraine, Dwek, Miriam, Earl, Helena M., Ekici, Arif B., Eliassen, A. Heather, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Figueroa, Jonine, Flesch-Janys, Dieter, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Galle, Eva, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., George, Angela, Georgoulias, Vassilios, Giles, Graham G., Glendon, Gord, Goldgar, David E., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan, Harkness, Elaine F., Harrington, Patricia A., Hart, Steven N., Hartikainen, Jaana M., Hein, Alexander, Hillemanns, Peter, Hiller, Louise, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Huang, Guanmengqian, Humphreys, Keith, Hunter, David J., Janni, Wolfgang, John, Esther M., Jones, Michael E., Jukkola-Vuorinen, Arja, Jung, Audrey, Kaaks, Rudolf, Kabisch, Maria, Kaczmarek, Katarzyna, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Kiiski, Johanna, I, Kitahara, Cari M., Knight, Julia A., Ko, Yon-Dschun, Koppert, Linetta B., Kosma, Veli-Matti, Kraft, Peter, Kristensen, Vessela N., Kruger, Ute, Kuehl, Tabea, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Li, Lian, Lindblom, Annika, Lindstrom, Sara, Linet, Martha, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Lubinski, Jan, Lux, Michael P., MacInnis, Robert J., Maierthaler, Melanie, Maishman, Tom, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, McLean, Catriona, Meindl, Alfons, Middha, Pooja, Miller, Nicola, Milne, Roger L., Moreno, Fernando, Mulligan, Anna Marie, Mulot, Claire, Nassir, Rami, Neuhausen, Susan L., Newman, William T., Nielsen, Sune F., Nordestgaard, Borge G., Norman, Aaron, Olsson, Hakan, Orr, Nick, Pankratz, V. Shane, Park-Simon, Tjoung-Won, Perez, Jose I. A., Perez-Barrios, Clara, Peterlongo, Paolo, Petridis, Christos, Pinchev, Mila, Prajzendanc, Karoliona, Prentice, Ross, Presneau, Nadege, Prokofieva, Darya, Pylkas, Katri, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rennert, Gadi, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Daniel F., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schumacher, Fredrick, Schwentner, Lukas, Scott, Rodney J., Scott, Christopher, Seynaeve, Caroline, Shah, Mitul, Simard, Jacques, Smeets, Ann, Sohn, Christof, Southey, Melissa C., Swerdlow, Anthony J., Talhouk, Aline, Tamimi, Rulla M., Tapper, William J., Teixeira, Manuel R., Tengstrom, Maria, Terry, Mary Beth, Thoene, Kathrin, Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Truong, Therese, Turman, Constance, Turnbull, Clare, Ulmer, Hans-Ulrich, Untch, Michael, Vachon, Celine, van Asperen, Christi J., van den Ouweland, Ans M. W., van Veen, Elke M., Wendt, Camilla, Whittemore, Alice S., Willett, Walter, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zhang, Yan, Easton, Douglas F., Fasching, Peter A., Nevanlinna, Heli, Eccles, Diana M., Pharoah, Paul D. P., Schmidt, Marjanka K., Escala-Garcia, Maria, Guo, Qi, Doerk, Thilo, Canisius, Sander, Keeman, Renske, Dennis, Joe, Beesley, Jonathan, Lecarpentier, Julie, Bolla, Manjeet K., Wang, Qin, Abraham, Jean, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Boeckx, Bram, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brentnall, Adam, Brinton, Louise, Broberg, Per, Brock, Ian W., Brucker, Sara Y., Burwinkel, Barbara, Caldas, Carlos, Caldes, Trinidad, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Chin, Suet-Feung, Clarke, Christine L., Cordina-Duverger, Emilie, Couch, Fergus J., Cox, David G., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dunn, Janet A., Dunning, Alison M., Durcan, Lorraine, Dwek, Miriam, Earl, Helena M., Ekici, Arif B., Eliassen, A. Heather, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Figueroa, Jonine, Flesch-Janys, Dieter, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Galle, Eva, Gapstur, Susan M., Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., George, Angela, Georgoulias, Vassilios, Giles, Graham G., Glendon, Gord, Goldgar, David E., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan, Harkness, Elaine F., Harrington, Patricia A., Hart, Steven N., Hartikainen, Jaana M., Hein, Alexander, Hillemanns, Peter, Hiller, Louise, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Huang, Guanmengqian, Humphreys, Keith, Hunter, David J., Janni, Wolfgang, John, Esther M., Jones, Michael E., Jukkola-Vuorinen, Arja, Jung, Audrey, Kaaks, Rudolf, Kabisch, Maria, Kaczmarek, Katarzyna, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Kiiski, Johanna, I, Kitahara, Cari M., Knight, Julia A., Ko, Yon-Dschun, Koppert, Linetta B., Kosma, Veli-Matti, Kraft, Peter, Kristensen, Vessela N., Kruger, Ute, Kuehl, Tabea, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Li, Lian, Lindblom, Annika, Lindstrom, Sara, Linet, Martha, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Lubinski, Jan, Lux, Michael P., MacInnis, Robert J., Maierthaler, Melanie, Maishman, Tom, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, McLean, Catriona, Meindl, Alfons, Middha, Pooja, Miller, Nicola, Milne, Roger L., Moreno, Fernando, Mulligan, Anna Marie, Mulot, Claire, Nassir, Rami, Neuhausen, Susan L., Newman, William T., Nielsen, Sune F., Nordestgaard, Borge G., Norman, Aaron, Olsson, Hakan, Orr, Nick, Pankratz, V. Shane, Park-Simon, Tjoung-Won, Perez, Jose I. A., Perez-Barrios, Clara, Peterlongo, Paolo, Petridis, Christos, Pinchev, Mila, Prajzendanc, Karoliona, Prentice, Ross, Presneau, Nadege, Prokofieva, Darya, Pylkas, Katri, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rennert, Gadi, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Daniel F., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schumacher, Fredrick, Schwentner, Lukas, Scott, Rodney J., Scott, Christopher, Seynaeve, Caroline, Shah, Mitul, Simard, Jacques, Smeets, Ann, Sohn, Christof, Southey, Melissa C., Swerdlow, Anthony J., Talhouk, Aline, Tamimi, Rulla M., Tapper, William J., Teixeira, Manuel R., Tengstrom, Maria, Terry, Mary Beth, Thoene, Kathrin, Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Truong, Therese, Turman, Constance, Turnbull, Clare, Ulmer, Hans-Ulrich, Untch, Michael, Vachon, Celine, van Asperen, Christi J., van den Ouweland, Ans M. W., van Veen, Elke M., Wendt, Camilla, Whittemore, Alice S., Willett, Walter, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zhang, Yan, Easton, Douglas F., Fasching, Peter A., Nevanlinna, Heli, Eccles, Diana M., Pharoah, Paul D. P., and Schmidt, Marjanka K.
Abstract: BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using similar to 10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). RESULTS: We did not find any variant associated with breast cancer-specific mortality at P<5 x 10(-8). For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 x 10(-7), hazard ratio [HR] = 0.88, 95% confidence interval [ CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7: rs67918676 (BFDP = 11%, P = 1.38 x 10(-7), HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. CONCLUSIONS: We uncovered germline variants on chromosome 7 at BFDP <15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.
Published: 2019
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24. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., Zheng, Wei, Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., and Zheng, Wei
Abstract: Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion
Published: 2016
Full Text: View/download PDF

25. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., Zheng, Wei, Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., and Zheng, Wei
Abstract: Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion
Published: 2016
Full Text: View/download PDF

26. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., Zheng, Wei, Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., and Zheng, Wei
Abstract: Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion
Published: 2016
Full Text: View/download PDF

27. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., Zheng, Wei, Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., and Zheng, Wei
Abstract: Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion
Published: 2016
Full Text: View/download PDF

28. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., Zheng, Wei, Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B., Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L., Milne, Roger L., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arason, Adalgeir, Arndt, Volker, Arun, Banu K., Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J., Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M., Clarke, Christine, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M., Doody, Michele, Dorfling, Cecilia M., Doerk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, Garcia-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Haiman, Christopher A., Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hartikainen, Jaana M., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Hogervorst, Frans B. L., Verhoef, Senno, Hendricks, Carolyn B., Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Kang, Daehee, Karlan, Beth Y., Kauppila, Saila, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Knight, Julia A., Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Le Marchand, Loic, Lee, Chuen Neng, Lee, Min Hyuk, Lester, Jenny, Li, Jingmei, Liljegren, Annelie, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Mai, Phuong L., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Nord, Silje, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olswold, Curtis, Osorio, Ana, Papi, Laura, Park-Simon, Tjoung-Won, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine M., Presneau, Nadege, Radice, Paolo, Rahman, Nazneen, Ramus, Susan J., Rashid, Muhammad Usman, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schuermann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha J., Shu, Xiao-Ou, Sigurdson, Alice, Singer, Christian F., Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla I., Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Teule, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, Turnbull, Clare, van den Ouweland, Ans M. W., van Rensburg, Elizabeth J., ven den Berg, David, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Whittemore, Alice S., Winqvist, Robert, Wong, Tien Y., Wu, Anna H., Yannoukakos, Drakoulis, Yu, Jyh-Cherng, Pharoah, Paul D. P., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison M., Simard, Jacques, Couch, Fergus J., Antoniou, Antonis C., Easton, Douglas F., and Zheng, Wei
Abstract: Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion
Published: 2016
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28 results on '"Hart, Steven"'

1. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

2. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

3. Breast Cancer Risk Factors and Survival by Tumor Subtype : Pooled Analyses from the Breast Cancer Association Consortium

4. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

5. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

6. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

7. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

8. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

9. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

10. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

11. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

12. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

13. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

14. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

15. CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

16. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

17. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

18. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

19. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

20. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

21. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

22. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

23. Genome-wide association study of germline variants and breast cancer-specific mortality

24. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

25. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

26. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

27. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

28. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

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28 results on '"Hart, Steven"'

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