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1. Additional file 4 of 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, B��rresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Br��ning, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Coll��e, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, D��rk, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garc��a-S��enz, Jos�� A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonz��lez-Neira, Anna, Aln��s, Grethe I. Grenaker, Grip, Mervi, Gu��nel, 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., Kr��ger, 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, H��kan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa V., Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylk��s, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, R��diger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Sch��ttker, 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., Garc��a-Closas, Montserrat, and Chatterjee, Nilanjan

Subjects
Data_FILES
Abstract

Additional file 4. Funding and Acknowledgement. This file contains the additional funding not included in the main text, the acknowledgments, and the names of the people in the collaboration groups.

Published
2022
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2. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author

Zhang, Haoyu, Ahearn, Thomas U, Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Jiang, Xia, O'Mara, Tracy A, Zhao, Ni, Bolla, Manjeet K, Dunning, Alison M, Dennis, Joe, Wang, Qin, Ful, Zumuruda Abu, Aittomäki, 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, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byers, Helen, Caldés, 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 BM, 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, Dörk, 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, García-Sáenz, José A, Gaudet, Mia M, Gayther, Simon A, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Häberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Hake, Christopher R, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Hillemanns, Peter, Hogervorst, Frans BL, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, Huebner, Hanna, Hulick, Peter J, Imyanitov, Evgeny N, kConFab Investigators, ABCTB Investigators, 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, MacInnis, 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, Nielsen, Finn C, Nikitina-Zake, Liene, Nodora, Jesse, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, 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, Rübner, Matthias, Rüdiger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P, Sawyer, Elinor J, Scheuner, Maren T, Schmutzler, Rita K, Schneeweiss, Andreas, Schoemaker, Minouk J, Schöttker, Ben, Schürmann, 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, EMBRACE Study, GEMO Study Collaborators, 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 AEM, Tomlinson, Ian, Torres, Diana, Troester, Melissa A, Truong, Thérèse, Tung, Nadine, Untch, Michael, Vachon, Celine M, van den Ouweland, Ans MW, 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 DP, Michailidou, Kyriaki, Antoniou, Antonis C, Schmidt, Marjanka K, Chenevix-Trench, Georgia, Easton, Douglas F, Chatterjee, Nilanjan, García-Closas, Montserrat, Barnes, Daniel [0000-0002-3781-7570], O'Mara, Tracy A [0000-0002-5436-3232], Dunning, Alison M [0000-0001-6651-7166], Dennis, Joe [0000-0003-4591-1214], Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Azzollini, Jacopo [0000-0002-9364-9778], Bojesen, Stig E [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Caldés, Trinidad [0000-0002-1038-5392], Calvello, Mariarosaria [0000-0003-2113-8503], Chanock, Stephen J [0000-0002-2324-3393], Claes, Kathleen BM [0000-0003-0841-7372], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dwek, Miriam [0000-0001-7184-2932], Ekici, Arif B [0000-0001-6099-7066], Fasching, Peter A [0000-0003-4885-8471], García-Sáenz, José A [0000-0001-6880-0301], Gayther, Simon A [0000-0001-7937-5443], Giles, Graham G [0000-0003-4946-9099], Greene, Mark H [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Harkness, Elaine F [0000-0001-6625-7739], Heemskerk-Gerritsen, Bernadette AM [0000-0002-9724-6693], Hollestelle, Antoinette [0000-0003-1166-1966], Huebner, Hanna [0000-0001-6889-1493], Hulick, Peter J [0000-0001-8397-4078], Jakimovska, Milena [0000-0002-1506-0669], Jakubowska, Anna [0000-0002-5650-0501], James, Paul [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Konstantopoulou, Irene [0000-0002-0470-0309], Larsson, Susanna C [0000-0003-0118-0341], Laurent-Puig, Pierre [0000-0001-8475-5459], Leslie, Goska [0000-0001-5756-6222], Lesueur, Fabienne [0000-0001-7404-4549], Lissowska, Jolanta [0000-0003-2695-5799], Matricardi, Laura [0000-0002-0241-1810], McLean, Catriona [0000-0002-0302-5727], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Newman, William G [0000-0002-6382-4678], Olopade, Olufunmilayo I [0000-0002-9936-1599], Orr, Nick [0000-0003-2866-942X], Parsons, Michael T [0000-0003-3242-8477], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Stone, Jennifer [0000-0001-5077-0124], Teixeira, Manuel R [0000-0002-4896-5982], Toland, Amanda E [0000-0002-0271-1792], Tomlinson, Ian [0000-0003-3037-1470], van Veen, Elke M [0000-0001-8618-2332], vanRensburg, Elizabeth J [0000-0003-2077-230X], Weitzel, Jeffrey N [0000-0001-6714-092X], Winqvist, Robert [0000-0003-0932-9104], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Zheng, Wei [0000-0003-1226-070X], Milne, Roger L [0000-0001-5764-7268], Kraft, Peter [0000-0002-4472-8103], Simard, Jacques [0000-0001-6906-3390], Pharoah, Paul DP [0000-0001-8494-732X], Michailidou, Kyriaki [0000-0001-7065-1237], Schmidt, Marjanka K [0000-0002-2228-429X], Easton, Douglas F [0000-0003-2444-3247], Chatterjee, Nilanjan [0000-0002-9060-008X], García-Closas, Montserrat [0000-0003-1033-2650], and Apollo - University of Cambridge Repository

Subjects
BRCA1 Protein, Case-Control Studies, Mutation, Humans, Breast Neoplasms, Female, Genetic Predisposition to Disease, Triple Negative Breast Neoplasms, Linkage Disequilibrium, Genome-Wide Association Study
Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. 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

Published
2020

3. What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420)

Author

French, David P., Astley, Susan, Brentnall, Adam R., Cuzick, Jack, Dobrashian, Richard, Duffy, Stephen W., Gorman, Louise S., Harkness, Elaine F., Harrison, Fiona, Harvie, Michelle, Howell, Anthony, Jerrison, Andrew, Machin, Matthew, Maxwell, Anthony J., McWilliams, Lorna, Payne, Katherine, Qureshi, Nadeem, Ruane, Helen, Sampson, Sarah, Stavrinos, Paula, Thorpe, Emma, Ulph, Fiona, Van Staa, Tjeerd, Woof, Victoria, and Evans, D. Gareth

Subjects
Cancer Research, Cost-Benefit Analysis, Anxiety, State Medicine, Study Protocol, 0302 clinical medicine, Breast cancer, Process analysis, Medicine, Mass Screening, Multicenter Studies as Topic, 030212 general & internal medicine, Family history, Child, Medical History Taking, Psychological impact, Mammographic density, Early Detection of Cancer, Clinical Trials as Topic, High risk, Multi site, MAMMOGRAPHIC DENSITY, Early detection, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, 030220 oncology & carcinogenesis, Screening, Female, Adult, medicine.medical_specialty, Adolescent, Breast Neoplasms, lcsh:RC254-282, Risk Assessment, Chemoprevention, 03 medical and health sciences, Young Adult, Genetics, Breast screening, Humans, Risk stratification, Protocol (science), Tyrer-Cuzick, business.industry, Health Plan Implementation, medicine.disease, United Kingdom, Family medicine, Feasibility Studies, Self Report, business, Program Evaluation
Abstract

Background In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict produces risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5 to Methods A non-randomised fully counterbalanced study design will be used, to include approximately equal numbers of women offered NHSBSP (n = 18,700) and BC-Predict (n = 18,700) from selected screening sites (n = 7). In the initial 8-month time period, women eligible for NHSBSP will be offered BC-Predict in four screening sites. Three screening sites will offer women usual NHSBSP. In the following 8-months the study sites offering usual NHSBSP switch to BC-Predict and vice versa. Key potential benefits including uptake of risk consultations, chemoprevention and additional screening will be obtained for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires, with embedded qualitative process analysis. A decision-analytic model-based cost-effectiveness analysis will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHSBSP. Discussion We will assess the feasibility of integrating BC-Predict into the NHSBSP, and identify the main uncertainties for a definitive evaluation of the clinical and cost-effectiveness of BC-Predict. Trial registration Retrospectively registered with clinicaltrials.gov (NCT04359420).

Published
2020

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

Author

Zhang, Haoyu, Ahearn, Thomas U, Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Jiang, Xia, O'Mara, Tracy A, Zhao, Ni, Bolla, Manjeet K, Dunning, Alison M, Dennis, Joe, Wang, Qin, Ful, Zumuruda Abu, Aittomäki, 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, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byers, Helen, Caldés, 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 BM, 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, Dörk, 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, García-Sáenz, José A, Gaudet, Mia M, Gayther, Simon A, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Häberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Hake, Christopher R, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Hillemanns, Peter, Hogervorst, Frans BL, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, Huebner, Hanna, Hulick, Peter J, Imyanitov, Evgeny N, KConFab Investigators, ABCTB Investigators, 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, MacInnis, 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, Nielsen, Finn C, Nikitina-Zake, Liene, Nodora, Jesse, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, 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, Rübner, Matthias, Rüdiger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P, Sawyer, Elinor J, Scheuner, Maren T, Schmutzler, Rita K, Schneeweiss, Andreas, Schoemaker, Minouk J, Schöttker, Ben, Schürmann, 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, EMBRACE Study, GEMO Study Collaborators, 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 AEM, Tomlinson, Ian, Torres, Diana, Troester, Melissa A, Truong, Thérèse, Tung, Nadine, Untch, Michael, Vachon, Celine M, Van Den Ouweland, Ans MW, 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 DP, Michailidou, Kyriaki, Antoniou, Antonis C, Schmidt, Marjanka K, Chenevix-Trench, Georgia, Easton, Douglas F, Chatterjee, Nilanjan, and García-Closas, Montserrat

Subjects
BRCA1 Protein, Case-Control Studies, Mutation, Humans, Breast Neoplasms, Female, Genetic Predisposition to Disease, Triple Negative Breast Neoplasms, Linkage Disequilibrium, Genome-Wide Association Study
Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. 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 × 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

5. Common 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, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collée, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., García-Sáenz, José A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, GrenakerAlnæs, Grethe I., Grip, Mervi, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Torres, 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., Krüger, 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, Håkan, Orr, Nick, Park-Simon, Tjoung-Won, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkäs, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Rüdiger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schöttker, 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., Terry, MaryBeth, 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., García-Closas, Montserrat, and Chatterjee, Nilanjan

Abstract

Background Genome-wide association studies have identified over 170 common breast cancer susceptibility variants, many of them with differential associations by estrogen receptor (ER). How these variants are related to other tumor features is unclear. Methods Analyses included 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 178 genotyped or imputed single nucleotide polymorphisms (SNPs). We used two-stage polytomous logistic regression models to evaluate SNPs 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 Nearly half of the SNPs (85 of 178) were associated with at least one tumor feature (false discovery rate

Published
2019
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7. Comparison of limited-contact dynamic compression plate and locking compression plate constructs for proximal interphalangeal joint arthrodesis in the horse

Author

Rocconi, Richard A., Carmalt, James L., Sampson, Sarah N., Elder, Steve H., and Gilbert, Eric E.

Subjects
Male, Forelimb, Cadaver, Animals, Arthrodesis, Scientific, Female, Joints, Horses, Bone Plates
Abstract

This study compared in vitro monotonic and cyclic mechanical properties of equine proximal interphalangeal joint arthrodeses stabilized using an open or closed technique combined with axial 4.5 mm narrow limited-contact dynamic compression plate (LC-DCP) or 4.5 mm narrow locking compression plate (LCP). Ten forelimb pairs were randomly assigned to LCP or LC-DCP groups. One limb in each pair was assigned to either open or closed technique. Limbs were tested for cyclic fatigue at 20 000 cycles and then single-cycle to failure under 3-point dorsopalmar bending. There was no significant difference in stiffness of constructs during cyclic fatigue testing or on force or stiffness at failure in single cycle to failure testing between open and closed techniques or between plate types. Both implants, surgical technique, or combinations thereof are suitable for clinical use. More work is necessary to define the interaction between implant type and surgical technique.

Published
2015

8. Additional file 1: Appendix 1. of Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort

Author

Brentnall, Adam, Harkness, Elaine, Astley, Susan, Donnelly, Louise, Stavrinos, Paula, Sampson, Sarah, Fox, Lynne, Sergeant, Jamie, Harvie, Michelle, Wilson, Mary, Beetles, Ursula, Soujanya Gadde, Yit Lim, Jain, Anil, Bundred, Sara, Barr, Nicola, Reece, Valerie, Howell, Anthony, Cuzick, Jack, and D. Evans

Subjects
body regions
Abstract

Density residual: description of methods. Appendix 2: Table S1. Univariate and multivariate performance of breast density and the Tyrer-Cuzick and Gail risk models, subgroup analysis by time of cancer diagnosis. (PDF 396 kb)

Published
2015
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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, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, NBCS Collaborators, Collée, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, ABCTB Investigators, KConFab/AOCS Investigators, 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, Krüger, 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, Håkan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkäs, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Rüdiger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P, Sawyer, Elinor J, Schmutzler, Rita K, Schoemaker, Minouk J, Schöttker, 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 HM, 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 DP, Schmidt, Marjanka K, García-Closas, Montserrat, and Chatterjee, Nilanjan

Subjects
Common breast cancer susceptibility variants, Risk, Receptor, ErbB-2, Genetic predisposition, Etiologic heterogeneity, Breast Neoplasms, 3. Good health, Breast cancer, Receptors, Estrogen, Biomarkers, Tumor, Humans, Female, Receptors, Progesterone, Genome-Wide Association Study
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.

10. Prospective evaluation of a breast-cancer risk model integrating classical risk factors and polygenic risk in 15 cohorts from six countries

Author

Hurson, Amber N, Pal Choudhury, Parichoy, Gao, Chi, Hüsing, Anika, Eriksson, Mikael, Shi, Min, Jones, Michael E, Evans, D Gareth R, Milne, Roger L, Gaudet, Mia M, Vachon, Celine M, Chasman, Daniel I, Easton, Douglas F, Schmidt, Marjanka K, Kraft, Peter, Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Scott, Christopher G, Carter, Brian D, Martin, Kara, Harkness, Elaine F, Brook, Mark N, Ahearn, Thomas U, Mavaddat, Nasim, Antoniou, Antonis C, Chang-Claude, Jenny, Simard, Jacques, Orr, Nick, Schoemaker, Minouk J, Swerdlow, Anthony J, Sampson, Sarah, Newman, William G, van Veen, Elke M, MacInnis, Robert J, Giles, Graham G, Southey, Melissa, Gapstur, Susan M, Winham, Stacey J, Brandt, Kathy, Norman, Aaron, Sandler, Dale P, Weinberg, Clarice R, Czene, Kamila, Gabrielson, Marike, Hall, Per, van Gils, Carla H, Khaw, Kay-Tee, Barrdahl, Myrto, Kaaks, Rudolf, Ridker, Paul M, and Buring, Julie E

Subjects
Adult, 0301 basic medicine, Multifactorial Inheritance, Epidemiology, Breast Neoplasms, Risk Assessment, Prospective evaluation, Risk category, Decile, Young Adult, 03 medical and health sciences, Risk model, 0302 clinical medicine, Breast cancer, Risk Factors, Germany, Breast Cancer, Humans, Medicine, Genetic Predisposition to Disease, Risk threshold, Aged, business.industry, General Medicine, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Risk stratification, Female, Polygenic risk score, business, Demography
Abstract

Background Rigorous evaluation of the calibration and discrimination of breast-cancer risk-prediction models in prospective cohorts is critical for applications under clinical guidelines. We comprehensively evaluated an integrated model incorporating classical risk factors and a 313-variant polygenic risk score (PRS) to predict breast-cancer risk. Methods Fifteen prospective cohorts from six countries with 239 340 women (7646 incident breast-cancer cases) of European ancestry aged 19–75 years were included. Calibration of 5-year risk was assessed by comparing expected and observed proportions of cases overall and within risk categories. Risk stratification for women of European ancestry aged 50–70 years in those countries was evaluated by the proportion of women and future cases crossing clinically relevant risk thresholds. Results Among women Conclusion Integrating a 313-variant PRS with classical risk factors can improve the identification of European-ancestry women at elevated risk who could benefit from targeted risk-reducing strategies under current clinical guidelines.

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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, B��rresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Br��ning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, NBCS Collaborators, Coll��e, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, D��rk, Thilo, Dwek, Miriam, Eccles, Diana M, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M, Garc��a-S��enz, Jos�� A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, Gonz��lez-Neira, Anna, Aln��s, Grethe I Grenaker, Grip, Mervi, Gu��nel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, ABCTB Investigators, KConFab/AOCS Investigators, 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, Kr��ger, 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, H��kan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylk��s, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, R��diger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P, Sawyer, Elinor J, Schmutzler, Rita K, Schoemaker, Minouk J, Sch��ttker, 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 HM, 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, Pharoah, Paul, Schmidt, Marjanka K, Garc��a-Closas, Montserrat, and Chatterjee, Nilanjan

Subjects
Common breast cancer susceptibility variants, Breast cancer, Genetic predisposition, Etiologic heterogeneity, 3. Good health, Research Article
Abstract

Funder: Genome Canada and the Canadian Institutes of Health Research, Funder: G��nome Qu��bec; doi: http://dx.doi.org/10.13039/100013062, Funder: Foundation for the National Institutes of Health; doi: http://dx.doi.org/10.13039/100000009, Funder: Center for Inherited Disease Research, Funder: Cancer Research UK, Funder: Odense University Hospital Research Foundation, Funder: National R&D Program for Cancer Control���Ministry of Health and Welfare, Funder: Italian Association for Cancer Research, Funder: Carol M. Baldwin Breast Cancer Research Fund; doi: http://dx.doi.org/10.13039/100002645, Funder: National Health and Medical Research Council, Funder: Deutsche Kinderkrebsstiftung; doi: http://dx.doi.org/10.13039/501100007311, Funder: European Union, Funder: National Institutes of Health; doi: http://dx.doi.org/10.13039/100000002, Funder: National Cancer Institute, Funder: Canadian Institutes of Health Research; doi: http://dx.doi.org/10.13039/501100000024, Funder: Susan G. Komen for the Cure, Komen Wyoming Affiliate; doi: http://dx.doi.org/10.13039/100005987, Funder: Ovarian Cancer Research Fund; doi: http://dx.doi.org/10.13039/100001282, Funder: National Cancer Institute (NCI), 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

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