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1. 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

2. Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study

Author

Javier Benitez, Sara Margolin, Diether Lambrechts, Alexandra J. van den Broek, Chen-Yang Shen, Veli-Matti Kosma, Matthias W. Beckmann, Siranoush Manoukian, Antoinette Hollestelle, Montserrat Garcia-Closas, Paul Brennan, Chiu-Chen Tseng, Marjanka K. Schmidt, Carolien H.M. van Deurzen, Peter A. Fasching, Melissa C. Southey, Manjeet K. Bolla, Robert Winqvist, Keitaro Matsuo, Douglas F. Easton, Carl Blomqvist, Adelheid Soubry, Paul D.P. Pharoah, Pascal Guénel, Jenna Lilyquist, Anna González-Neira, Hidemi Ito, Daehee Kang, Thérèse Truong, Fergus J. Couch, Renske Keeman, Kenneth Muir, Caroline Seynaeve, Katri Pylkäs, Simon S. Cross, Per Hall, Olivier Brouckaert, Roger L. Milne, Cheng Har Yip, Qin Wang, Sten Cornelissen, Anja Rudolph, Kamila Czene, Artitaya Lophatananon, Mikael Eriksson, Xiao-Ou Shu, Jonine D. Figueroa, Julia A. Knight, Arto Mannermaa, Jyh-Cherng Yu, Hans Wildiers, John L. Hopper, Wei Zheng, Jingmei Li, Rob A. E. M. Tollenaar, Anthony J. Swerdlow, Hermann Brenner, Henrik Flyger, Patrick Neven, Georgia Chenevix-Trench, Irene L. Andrulis, Paolo Peterlongo, Ji Yeob Choi, Annouschka Laenen, Annika Lindblom, Hiltrud Brauch, Anna H. Wu, Heli Nevanlinna, Michael Jones, Angela Cox, Volker Arndt, Soo-Hwang Teo, Jenny Chang-Claude, Stig E. Bojesen, Graham G. Giles, Suleeporn Saajrang, School of Medicine / Clinical Medicine, Wang, Jean [0000-0002-9139-0627], Benitez, Javier [0000-0002-0923-7202], Blomqvist, Carl [0000-0003-3041-1938], Brauch, Hiltrud [0000-0001-7531-2736], Brenner, Hermann [0000-0002-6129-1572], Chenevix-Trench, Georgia [0000-0002-1878-2587], Cox, Angela [0000-0002-5138-1099], Eriksson, Mikael [0000-0001-8135-4270], González-Neira, Anna [0000-0002-5421-2020], Guénel, Pascal [0000-0002-8359-518X], Jones, Michael [0000-0001-7479-3451], Li, Jingmei [0000-0001-8587-7511], Matsuo, Keitaro [0000-0003-1761-6314], Peterlongo, Paolo [0000-0001-6951-6855], Pylkäs, Katri [0000-0002-2449-0521], Southey, Melissa C [0000-0002-6313-9005], Swerdlow, Anthony [0000-0001-5550-4159], Truong, Thérèse [0000-0002-2943-6786], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Lambrechts, Diether [0000-0002-3429-302X], Apollo - University of Cambridge Repository, Medical Oncology, Pathology, Department of Oncology, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, HUS Comprehensive Cancer Center, Unión Europea. Comisión Europea. 7 Programa Marco, Cancer Research UK (Reino Unido), NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), New South Wales Cancer Council (Reino Unido), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Agence Nationale de la Recherche (Francia), French Agency for Food, Environmental and Occupational Health & Safety (Francia), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Centro de Investigación Biomedica en Red - CIBER, Federal Ministry of Education & Research (Alemania), Cancer Society of Finland, Ministry of Education, Culture, Sports, Science, and Technology (Japón), Japan Agency for Medical Research and Development, United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Ministry of Higher Education (Malasia), Biomedical Research Council (Singapore), National Institutes of Health (Estados Unidos), and National Research Foundation of Korea

Subjects
0301 basic medicine, Oncology, Triple Negative Breast Neoplasms, Cohort Studies, 0302 clinical medicine, HORMONE-RECEPTOR STATUS, Medizinische Fakultät, Risk Factors, Odds Ratio, Young adult, Reproductive History, POPULATION, Age at menarche, education.field_of_study, WOMEN, ASSOCIATION, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Parity, PREGNANCY, 030220 oncology & carcinogenesis, Age at breast cancer diagnosis, kConFab, Menarche, Female, Cohort study, Research Article, Adult, medicine.medical_specialty, 3122 Cancers, Population, Breast Neoplasms, DIAGNOSIS, lcsh:RC254-282, Risk Assessment, MENARCHE, 1ST BIRTH, 03 medical and health sciences, Young Adult, AGE, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Journal Article, medicine, Biomarkers, Tumor, Humans, ddc:610, education, Aged, Gynecology, Pregnancy, business.industry, Odds ratio, medicine.disease, 030104 developmental biology, Age at first full-time pregnancy, Breast cancer subtype, business
Abstract

Background Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. Methods We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. Results Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16–1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01–2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45–1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70–0.88, p, published version, peerReviewed

Published
2017
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