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

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Date
2020-05-18Authors
Bogdanova, Natalia V.Bojesen, Stig E.
Bonanni , Bernardo
Bondavalli, Davide
Borg, Ake
Brauch, Hiltrud
Brenner, Hermann
Briceño Balcázar, 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 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.
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 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.
kConFab Investigators
ABCTB Investigators
Isaacs, Claudine
Izatt, Louise
Jager, Agnes
Jakimovska, Milena
Jakubowska, Anna
James, Paul A.
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, Sergio V.
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, Gad
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.
Szabova, Elena
Tamimi, Rulla M.
Tapper, William J.
Taylor, Jack A.
Teixeira, Manuel R.
Terry, Mary Beth
Thomassen, Mads
Thull, Darcy L.
Tischkowitz, Marc
Toland, Amanda E.
Tollenaar, Rob A.E.M.
Tomlinson, Ian
Torres-López, Diana María
Troester, Melissa A.
Truong, Thérèse
Tung, Nadine
Untch, Michae
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
García-Closas, Montserrat
Corporate Author(s)
Pontificia Universidad Javeriana. Facultad de Medicina. Instituto de Genética Humana. Grupo de investigación Instituto de Genética Humana
Type
Artículo de revista
ISSN
1061-4036 / 1546-1718 (Electrónico)
COAR
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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.
Community
Mujeres con Cáncer de mamaLink to the resource
https://revistas.javeriana.edu.co/index.php/revPsycho/article/view/21878Source
Nature Genetics; Volumen 52 Número 6 , Páginas 572 - 581 (2020)
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