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

• DOI: 10.1186/s13058-021-01484-x
• Publication Date: 2022-01-04T11:05:09Z
• Authors: Thomas U. Ahearn; Haoyu Zhang; Kyriaki Michailidou; Roger L. Milne; Manjeet K. Bolla; Joe Dennis; Alison M. Dunning; Michael Lush; Qin Wang; Irene L. Andrulis; Hoda Anton-Culver; Volker Arndt; Kristan J. Aronson; Paul L. Auer; Annelie Augustinsson; Adinda Baten; Heiko Becher; Sabine Behrens; Javier Benitez; Marina Bermisheva; Carl Blomqvist; Stig E. Bojesen; Bernardo Bonanni; Anne-Lise Børrese...; Hiltrud Brauch; Hermann Brenner; Angela Brooks-Wilson; Thomas Brüning; Barbara Burwinkel; Saundra S. Buys; Federico Canzian; Jose E. Castelao; Jenny Chang-Claude; Stephen J. Chanock; Georgia Chenevix-...; Christine L. Clarke; ; Kristine K. Sahlberg; Lars Ottestad; Rolf Kåresen; Ellen Schlichting; Marit Muri Holmen; Toril Sauer; Vilde Haakensen; Olav Engebråten; Bjørn Naume; Alexander Fosså; Cecile E. Kiserud; Kristin V. Reiner...; Åslaug Helland; Margit Riis; Jürgen Geisler; J. Margriet Collée; Angela Cox; Simon S. Cross; Kamila Czene; Mary B. Daly; Peter Devilee; Thilo Dörk; Miriam Dwek; Diana M. Eccles; D. Gareth Evans; Peter A. Fasching; Jonine Figueroa; Giuseppe Floris; Manuela Gago-Domi...; Susan M. Gapstur; José A. García-Sáenz; Mia M. Gaudet; Graham G. Giles; Mark S. Goldberg; Anna González-Neira; Grethe I. Grenake...; Mervi Grip; Pascal Guénel; Christopher A. Ha...; Per Hall; Ute Hamann; Elaine F. Harkness; Bernadette A. M. ...; Bernd Holleczek; Antoinette Holles...; Maartje J. Hooning; Robert N. Hoover; John L. Hopper; Anthony Howell; ; Christine Clarke; Rosemary Balleine; Robert Baxter; Stephen Braye; Jane Carpenter; Jane Dahlstrom; John Forbes; CSoon Lee; Deborah Marsh; Adrienne Morey; Nirmala Pathmanathan; Rodney Scott; Peter Simpson; Allan Spigelman; Nicholas Wilcken; Desmond Yip; Nikolajs Zeps; ; Stephen Fox; Ian Campbell; David Bowtell; Georgia Chenevix-...; Amanda Spurdle; Penny Webb; Anna de Fazio; Margaret Tassell; Judy Kirk; Geoff Lindeman; Melanie Price; Melissa Southey; Roger Milne; Sid Deb; Milena Jakimovska; Anna Jakubowska; Esther M. John; Michael E. Jones; Audrey Jung; Rudolf Kaaks; Saila Kauppila; Renske Keeman; Elza Khusnutdinova; Cari M. Kitahara; Yon-Dschun Ko; Stella Koutros; Vessela N. Kriste...; Ute Krüger; Katerina Kubelka-...; Allison W. Kurian; Kyriacos Kyriacou; Diether Lambrechts; Derrick G. Lee; Annika Lindblom; Martha Linet; Jolanta Lissowska; Ana Llaneza; Wing-Yee Lo; Robert J. MacInnis; Arto Mannermaa; Mehdi Manoochehri; Sara Margolin; Maria Elena Martinez; Catriona McLean; Alfons Meindl; Usha Menon; Heli Nevanlinna; William G. Newman; Jesse Nodora; Kenneth Offit; Håkan Olsson; Nick Orr; Tjoung-Won Park-S...; Alpa V. Patel; Julian Peto; Guillermo Pita; Dijana Plaseska-K...; Ross Prentice; Kevin Punie; Katri Pylkäs; Paolo Radice; Gad Rennert; Atocha Romero; Thomas Rüdiger; Emmanouil Saloustros; Sarah Sampson; Dale P. Sandler; Elinor J. Sawyer; Rita K. Schmutzler; Minouk J. Schoemaker; Ben Schöttker; Mark E. Sherman; Xiao-Ou Shu; Snezhana Smichkoska; Melissa C. Southey; John J. Spinelli; Anthony J. Swerdlow; Rulla M. Tamimi; William J. Tapper; Jack A. Taylor; Lauren R. Teras; Mary Beth Terry; Diana Torres; Melissa A. Troester; Celine M. Vachon; Carolien H. M. va...; Elke M. van Veen; Philippe Wagner; Clarice R. Weinberg; Camilla Wendt; Jelle Wesseling; Robert Winqvist; Alicja Wolk; Xiaohong R. Yang; Wei Zheng; Fergus J. Couch; Jacques Simard; Peter Kraft; Douglas F. Easton; Paul D. P. Pharoah; Marjanka K. Schmidt; Montserrat García...; Nilanjan Chatterjee
• Keywords: Genome-wide Association Study; Surgical oncology; Genetic Association

Abstract Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants differential associations by estrogen receptor (ER) status, but how relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive cases 95,762 controls European ancestry data on 173 in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate relation (ER, progesterone (PR), human epidermal growth factor 2 (HER2) grade) adjusting for each other, intrinsic-like subtypes. Results Eighty-five were associated at least one feature (false discovery rate < 5%), most commonly ER grade, followed PR HER2. Models found nearly all (83 85) p 0.05 risk luminal-like subtype, approximately half (41 the non-luminal including 32 triple-negative (TN) disease. Ten different magnitude. Five luminal A-like TN opposite directions. Conclusion This report demonstrates a high level complexity etiology heterogeneity can inform investigations subtype-specific prediction.