Author: "Eccles, Diana M." / Publisher: hannover med sch, gynaecol res unit, hannover, germany. - Searchworks@Jio Institute Digital Library Search Results

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35 results on '"Eccles, Diana M."'

1. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

Author: Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., Michailidou, Kyriaki, Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., and Michailidou, Kyriaki
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Published: 2023
Full Text: View/download PDF

2. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

Author: Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., Michailidou, Kyriaki, Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., and Michailidou, Kyriaki
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Published: 2023
Full Text: View/download PDF

3. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

Author: Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., Michailidou, Kyriaki, Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., and Michailidou, Kyriaki
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Published: 2023
Full Text: View/download PDF

4. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

Author: Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., Michailidou, Kyriaki, Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., and Michailidou, Kyriaki
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Published: 2023
Full Text: View/download PDF

5. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

Author: Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., Michailidou, Kyriaki, Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., and Michailidou, Kyriaki
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Published: 2023
Full Text: View/download PDF

6. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

7. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

8. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
Full Text: View/download PDF

9. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
Full Text: View/download PDF

10. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
Full Text: View/download PDF

11. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
Full Text: View/download PDF

12. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
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13. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
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14. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmana, Judith, Bandera, Elisa, V, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia, V, Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dork, Thilo, du Bois, Andreas, Durst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, ReneeT, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Group, Opal Study, Group, AOCS, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Hogdall, Estrid, Hogdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th, John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., KimMatsuno, Rayna, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo, I, Olson, Sara H., Olsson, Hakan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamarina, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., BethTerry, Mary, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Nieuwenhuysen, ElsVan, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022
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15. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collee, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonzalez-Neira, Anna, Alnaes, Grethe I. Grenaker, Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kruger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Hakan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa, V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schottker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garcia-Closas, Montserrat, and Chatterjee, Nilanjan
Abstract: Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Published: 2022
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16. 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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17. 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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18. 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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19. 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
Full Text: View/download PDF

20. 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
Full Text: View/download PDF

21. 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

22. 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

23. 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

24. 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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25. 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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26. 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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27. 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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28. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author: Zhan, Haoyu, Ahearn, Thomas U., Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Hang, Xia, O'Mara, Tracy A., Zhao, Ni, Bolla, Manjeet K., Dunning, Alison M., Dennis, Joe, Wang, Qin, Abu Ful, Zumuruda, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Arun, Banu K., Auer, Paul L., Azzollini, Jacopo, Barrowdale, Daniel, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Bondavalli, Davide, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Byers, Helen, Caldes, Trinidad, Caligo, Maria A., Calvello, Mariarosaria, Campa, Daniele, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Christiaens, Melissa, Christiansen, Hans, Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Cornelissen, Sten, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Domchek, Susan M., Doerk, Thilo, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Foretova, Lenka, Fostira, Florentia, Friedman, Eitan, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Gronwald, Jacek, Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hake, Christopher R., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Hillemanns, Peter, Hogervorst, Frans B. L., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Huebner, Hanna, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khan, Sofia, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Konstantopoulou, Irene, Koppert, Linetta B., Koutros, Stella, Kristensen, Vessela N., Laenkholm, Anne-Vibeke, Lambrechts, Diether, Larsson, Susanna C., Laurent-Puig, Pierre, Lazaro, Conxi, Lazarova, Emilija, Lejbkowicz, Flavio, Leslie, Goska, Lesueur, Fabienne, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loud, Jennifer T., Lubinski, Jan, Lukomska, Alicja, Maclnnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matricardi, Laura, McGuffog, Lesley, McLean, Catriona, Mebirouk, Noura, Meindl, Alfons, Menon, Usha, Miller, Austin, Mingazheva, Elvira, Montagna, Marco, Mulligan, Anna Marie, Mulot, Claire, Muranen, Taru A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Newman, William G., Nielsens, Finn C., Nikitina-Zake, Liene, Nodora, Jesse, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, I, Olsson, Hakan, Orr, Nick, Papi, Laura, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T., Peissel, Bernard, Peixoto, Ana, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Phillips, Kelly-Anne, Piedmonte, Marion, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Prokofyeva, Darya, Rack, Brigitte, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Risch, Harvey A., Romero, Atocha, Rookus, Matti A., Ruebner, Matthias, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Scheuner, Maren T., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schoettker, Ben, Schuermann, Peter, Senter, Leigha, Sharma, Priyanka, Sherman, Mark E., Shu, Xiao-Ou, Singer, Christian F., Smichkoska, Snezhana, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony J., Szabo, Csilla, I, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teixeira, Manuel R., Terry, MaryBeth, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Tung, Nadine, Untch, Michael, Vachon, Celine M., van den Ouweland, Ans M. W., van der Kolk, Lizet E., van Veen, Elke M., vanRensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Zorn, Kristin K., Milne, Roger L., Kraft, Peter, Simard, Jacques, Pharoah, Paul D. P., Michailidou, Kyriaki, Antoniou, Antonis C., Schmidt, Marjanka K., Chenevix-Trench, Georgia, Easton, Douglas F., Chatterjee, Nilanjan, Garcia-Closas, Montserrat, Zhan, Haoyu, Ahearn, Thomas U., Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Hang, Xia, O'Mara, Tracy A., Zhao, Ni, Bolla, Manjeet K., Dunning, Alison M., Dennis, Joe, Wang, Qin, Abu Ful, Zumuruda, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Arun, Banu K., Auer, Paul L., Azzollini, Jacopo, Barrowdale, Daniel, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Bondavalli, Davide, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Byers, Helen, Caldes, Trinidad, Caligo, Maria A., Calvello, Mariarosaria, Campa, Daniele, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Christiaens, Melissa, Christiansen, Hans, Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Cornelissen, Sten, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Domchek, Susan M., Doerk, Thilo, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Foretova, Lenka, Fostira, Florentia, Friedman, Eitan, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Gronwald, Jacek, Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hake, Christopher R., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Hillemanns, Peter, Hogervorst, Frans B. L., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Huebner, Hanna, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khan, Sofia, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Konstantopoulou, Irene, Koppert, Linetta B., Koutros, Stella, Kristensen, Vessela N., Laenkholm, Anne-Vibeke, Lambrechts, Diether, Larsson, Susanna C., Laurent-Puig, Pierre, Lazaro, Conxi, Lazarova, Emilija, Lejbkowicz, Flavio, Leslie, Goska, Lesueur, Fabienne, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loud, Jennifer T., Lubinski, Jan, Lukomska, Alicja, Maclnnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matricardi, Laura, McGuffog, Lesley, McLean, Catriona, Mebirouk, Noura, Meindl, Alfons, Menon, Usha, Miller, Austin, Mingazheva, Elvira, Montagna, Marco, Mulligan, Anna Marie, Mulot, Claire, Muranen, Taru A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Newman, William G., Nielsens, Finn C., Nikitina-Zake, Liene, Nodora, Jesse, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, I, Olsson, Hakan, Orr, Nick, Papi, Laura, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T., Peissel, Bernard, Peixoto, Ana, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Phillips, Kelly-Anne, Piedmonte, Marion, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Prokofyeva, Darya, Rack, Brigitte, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Risch, Harvey A., Romero, Atocha, Rookus, Matti A., Ruebner, Matthias, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Scheuner, Maren T., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schoettker, Ben, Schuermann, Peter, Senter, Leigha, Sharma, Priyanka, Sherman, Mark E., Shu, Xiao-Ou, Singer, Christian F., Smichkoska, Snezhana, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony J., Szabo, Csilla, I, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teixeira, Manuel R., Terry, MaryBeth, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Tung, Nadine, Untch, Michael, Vachon, Celine M., van den Ouweland, Ans M. W., van der Kolk, Lizet E., van Veen, Elke M., vanRensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Zorn, Kristin K., Milne, Roger L., Kraft, Peter, Simard, Jacques, Pharoah, Paul D. P., Michailidou, Kyriaki, Antoniou, Antonis C., Schmidt, Marjanka K., Chenevix-Trench, Georgia, Easton, Douglas F., Chatterjee, Nilanjan, and Garcia-Closas, Montserrat
Abstract: Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
Published: 2020
Full Text: View/download PDF

29. 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

30. 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

31. 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

32. 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

33. 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

34. Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis

Author: Shu, Xiang, Wu, Lang, Khankari, Nikhil K., Shu, Xiao-Ou, Wang, Thomas J., Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Milne, Roger L., Schmidt, Marjanka K., Pharoah, Paul D. P., Andrulis, Irene L., Hunter, David J., Simard, Jacques, Easton, Douglas F., Zheng, Wei, Alicia, Beeghly-Fadiel J., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Barrdahl, Myrto, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y., Bruning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldes, Trinidad, Canzian, Federico, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, David G., Cox, Angela, Cross, Simon S., Cunningham, Julie M., Czene, Kamila, Daly, Mary B., Doheny, Kimberly F., Dork, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dunning, Alison M., Dwek, Miriam, Earp, H. Shelton, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fachal, Laura, Fasching, Peter A., Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Ghoussaini, Maya, Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, He, Wei, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hogervorst, Frans B., Hollestelle, Antoinette, Hoover, Robert N., Hopper, John L., Howell, Anthony, Huang, Guanmengqian, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Johnson, Nichola, Jones, Kristine, Jung, Audrey, Kaaks, Rudolf, Kabisch, Maria, Kerin, Michael J., Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lambrechts, Diether, Le Marchand, Loic, Lindstrom, Sara, Linet, Martha S., Lissowska, Jolanta, Loibl, Sibylle, Lubinski, Jan, Luccarini, Craig, Lux, Michael P., Maishman, Tom, Kostovska, Ivana Maleva, Mannermaa, Arto, Manoukian, Siranoush, Manson, Joann E., Margolin, Sara, Mavroudis, Dimitrios, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Meyer, Jeffery, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Newman, William T., Nielsen, Sune F., Nordestgaard, Borge G., Olopade, Olufunmilayo I., Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Olswol, Curtis, Orr, Nick, Perou, Charles M., Peto, Julian, Plaseska-Karanfilska, Dijana, Prentice, Ross, Presneau, Nadege, Pylkas, Katri, Rack, Brigitte, Radice, Paolo, Rahman, Nazneen, Rennert, Gadi, Rennert, Hedy S., Romero, Atocha, Romm, Jane, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Rodney J., Scott, Christopher, Seal, Sheila, Seynaeve, Caroline, Smeets, Ann, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla, Tapper, William, Taylor, Jack A., Terry, Mary Beth, Tessier, Daniel C., Thone, Kathrin, Tollenaar, Rob A. E. M., Torres, Diana, Troester, Melissa A., Truong, Therese, Untch, Michael, Vachon, Celine, Van Den Berg, David, van den Ouweland, Ans M. W., van Veen, Elke M., Vincent, Daniel, Waisfisz, Quinten, Weinberg, Clarice R., Wendt, Camilla, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Xia, Lucy, Yang, Xiaohong R., Ziogas, Argyrios, Ziv, Elad, Shu, Xiang, Wu, Lang, Khankari, Nikhil K., Shu, Xiao-Ou, Wang, Thomas J., Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Milne, Roger L., Schmidt, Marjanka K., Pharoah, Paul D. P., Andrulis, Irene L., Hunter, David J., Simard, Jacques, Easton, Douglas F., Zheng, Wei, Alicia, Beeghly-Fadiel J., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Barrdahl, Myrto, Baynes, Caroline, Freeman, Laura E. Beane, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y., Bruning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldes, Trinidad, Canzian, Federico, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, David G., Cox, Angela, Cross, Simon S., Cunningham, Julie M., Czene, Kamila, Daly, Mary B., Doheny, Kimberly F., Dork, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dunning, Alison M., Dwek, Miriam, Earp, H. Shelton, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fachal, Laura, Fasching, Peter A., Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Closas, Montserrat, Gaudet, Mia M., Ghoussaini, Maya, Giles, Graham G., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, He, Wei, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hogervorst, Frans B., Hollestelle, Antoinette, Hoover, Robert N., Hopper, John L., Howell, Anthony, Huang, Guanmengqian, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Johnson, Nichola, Jones, Kristine, Jung, Audrey, Kaaks, Rudolf, Kabisch, Maria, Kerin, Michael J., Khusnutdinova, Elza, Kitahara, Cari M., Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lambrechts, Diether, Le Marchand, Loic, Lindstrom, Sara, Linet, Martha S., Lissowska, Jolanta, Loibl, Sibylle, Lubinski, Jan, Luccarini, Craig, Lux, Michael P., Maishman, Tom, Kostovska, Ivana Maleva, Mannermaa, Arto, Manoukian, Siranoush, Manson, Joann E., Margolin, Sara, Mavroudis, Dimitrios, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Meyer, Jeffery, Mulligan, Anna Marie, Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Newman, William T., Nielsen, Sune F., Nordestgaard, Borge G., Olopade, Olufunmilayo I., Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Olswol, Curtis, Orr, Nick, Perou, Charles M., Peto, Julian, Plaseska-Karanfilska, Dijana, Prentice, Ross, Presneau, Nadege, Pylkas, Katri, Rack, Brigitte, Radice, Paolo, Rahman, Nazneen, Rennert, Gadi, Rennert, Hedy S., Romero, Atocha, Romm, Jane, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schneeweiss, Andreas, Scott, Rodney J., Scott, Christopher, Seal, Sheila, Seynaeve, Caroline, Smeets, Ann, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J., Tamimi, Rulla, Tapper, William, Taylor, Jack A., Terry, Mary Beth, Tessier, Daniel C., Thone, Kathrin, Tollenaar, Rob A. E. M., Torres, Diana, Troester, Melissa A., Truong, Therese, Untch, Michael, Vachon, Celine, Van Den Berg, David, van den Ouweland, Ans M. W., van Veen, Elke M., Vincent, Daniel, Waisfisz, Quinten, Weinberg, Clarice R., Wendt, Camilla, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Xia, Lucy, Yang, Xiaohong R., Ziogas, Argyrios, and Ziv, Elad
Abstract: Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2
Published: 2019
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35. 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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35 results on '"Eccles, Diana M."'

1. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

2. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

3. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

4. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

5. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

6. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

7. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

8. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

9. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

10. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

11. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

12. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

13. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

14. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

15. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

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

17. 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

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

19. 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

20. 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

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

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

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

24. 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

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

26. 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

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

28. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

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

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

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

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

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

34. Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis

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

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35 results on '"Eccles, Diana M."'

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