Common variants in breast cancer risk loci predispose to distinct tumor subtypes
Creators: name: Ahearn, Thomas U.
name: Zhang, Haoyu
name: Michailidou, Kyriaki
name: Milne, Roger L.
name: Bolla, Manjeet K.
name: Dennis, Joe
name: Dunning, Alison M.
name: Lush, Michael
name: Wang, Qin
name: Andrulis, Irene L.
name: Anton-Culver, Hoda
name: Arndt, Volker
name: Aronson, Kristan J.
name: Auer, Paul L.
name: Augustinsson, Annelie
name: Baten, Adinda
name: Becher, Heiko
name: Behrens, Sabine
name: Benitez, Javier
name: Bermisheva, Marina
name: Blomqvist, Carl
name: Bojesen, Stig E.
name: Bonanni, Bernardo
name: Børresen-Dale, Anne-Lise
name: Brauch, Hiltrud
name: Brenner, Hermann
name: Brooks-Wilson, Angela
name: Brüning, Thomas
name: Burwinkel, Barbara
name: Buys, Saundra S.
name: Canzian, Federico
name: Castelao, Jose E.
name: Chang-Claude, Jenny
name: Chanock, Stephen J.
name: Chenevix-Trench, Georgia
name: Clarke, Christine L.
name: Collée, J. M.
name: Cox, Angela
name: Cross, Simon S.
name: Czene, Kamila
name: Daly, Mary B.
name: Devilee, Peter
name: Dörk, Thilo
name: Dwek, Miriam
name: Eccles, Diana M.
name: Evans, D. G.
name: Fasching, Peter A.
name: Figueroa, Jonine
name: Floris, Giuseppe
name: Gago-Dominguez, Manuela
name: Gapstur, Susan M.
name: García-Sáenz, José A.
name: Gaudet, Mia M.
name: Giles, Graham G.
name: Goldberg, Mark S.
name: González-Neira, Anna
name: Alnæs, Grethe I. G.
name: Grip, Mervi
name: Guénel, Pascal
name: Haiman, Christopher A.
name: Hall, Per
name: Hamann, Ute
name: Harkness, Elaine F.
name: Heemskerk-Gerritsen, Bernadette A. M.
name: Holleczek, Bernd
name: Hollestelle, Antoinette
name: Hooning, Maartje J.
name: Hoover, Robert N.
name: Hopper, John L.
name: Howell, Anthony
name: Jakimovska, Milena
name: Jakubowska, Anna
name: John, Esther M.
name: Jones, Michael E.
name: Jung, Audrey
name: Kaaks, Rudolf
name: Kauppila, Saila
name: Keeman, Renske
name: Khusnutdinova, Elza
name: Kitahara, Cari M.
name: Ko, Yon-Dschun
name: Koutros, Stella
name: Kristensen, Vessela N.
name: Krüger, Ute
name: Kubelka-Sabit, Katerina
name: Kurian, Allison W.
name: Kyriacou, Kyriacos
name: Lambrechts, Diether
name: Lee, Derrick G.
name: Lindblom, Annika
name: Linet, Martha
name: Lissowska, Jolanta
name: Llaneza, Ana
name: Lo, Wing-Yee
name: MacInnis, Robert J.
name: Mannermaa, Arto
name: Manoochehri, Mehdi
name: Margolin, Sara
name: Martinez, Maria E.
name: McLean, Catriona
name: Meindl, Alfons
name: Menon, Usha
name: Nevanlinna, Heli
name: Newman, William G.
name: Nodora, Jesse
name: Offit, Kenneth
name: Olsson, Håkan
name: Orr, Nick
name: Park-Simon, Tjoung-Won
name: Patel, Alpa V.
name: Peto, Julian
name: Pita, Guillermo
name: Plaseska-Karanfilska, Dijana
name: Prentice, Ross
name: Punie, Kevin
name: Pylkäs, Katri
name: Radice, Paolo
name: Rennert, Gad
name: Romero, Atocha
name: Rüdiger, Thomas
name: Saloustros, Emmanouil
name: Sampson, Sarah
name: Sandler, Dale P.
name: Sawyer, Elinor J.
name: Schmutzler, Rita K.
name: Schoemaker, Minouk J.
name: Schöttker, Ben
name: Sherman, Mark E.
name: Shu, Xiao-Ou
name: Smichkoska, Snezhana
name: Southey, Melissa C.
name: Spinelli, John, 1955-
name: Swerdlow, Anthony J.
name: Tamimi, Rulla M.
name: Tapper, William J.
name: Taylor, Jack A.
name: Teras, Lauren R.
name: Terry, Mary B.
name: Torres, Diana
name: Troester, Melissa A.
name: Vachon, Celine M.
name: Van Deurzen, Carolien H. M.
name: Van Veen, Elke M.
name: Wagner, Philippe
name: Weinberg, Clarice R.
name: Wendt, Camilla
name: Wesseling, Jelle
name: Winqvist, Robert
name: Wolk, Alicja
name: Yang, Xiaohong R.
name: Zheng, Wei
name: Couch, Fergus J.
name: Simard, Jacques
name: Kraft, Peter
name: Easton, Douglas F.
name: Pharoah, Paul D. P.
name: Schmidt, Marjanka K.
name: García-Closas, Montserrat
name: Chatterjee, Nilanjan
Publisher: name: BioMed Central
Year: 2022

description: 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 &lt; 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 &lt; 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.