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

Ahearn TU, Zhang H, Michailidou K, Milne RL, Bolla MK, Dennis J, Dunning AM, Lush M, Wang Q, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Auer PL, Augustinsson A, Baten A, Becher H, Behrens S, Benitez J, Bermisheva M, Blomqvist C, Bojesen SE, Bonanni B, Borresen-Dale AL, Brauch H, Brenner H, Brooks-Wilson A, Bruening T, Burwinkel B, Buys SS, Canzian F, Castelao JE, Chang-Claude J, Chanock SJ, Chenevix-Trench G, Clarke CL, Collee JM, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Dork T, Dwek M, Eccles DM, Evans DG, Fasching P, Figueroa J, Floris G, Gago-Dominguez M, Gapstur SM, Garcia-Saenz JA, Gaudet MM, Giles GG, Goldberg MS, Gonzalez-Neira A, Alnaes GIG, Grip M, Guenel P, Haiman CA, Hall P, Hamann U, Harkness EF, Heemskerk-Gerritsen BAM, Holleczek B, Hollestelle A, Hooning MJ, Hoover RN, Hopper JL, Howell A, Jakimovska M, Jakubowska A, John EM, Jones ME, Jung A, Kaaks R, Kauppila S, Keeman R, Khusnutdinova E, Kitahara CM, Ko YD, Koutros S, Kristensen VN, Kruger U, Kubelka-Sabit K, Kurian AW, Kyriacou K, Lambrechts D, Lee DG, Lindblom A, Linet M, Lissowska J, Llaneza A, Lo WY, Macinnis RJ, Mannermaa A, Manoochehri M, Margolin S, Martinez ME, Mclean C, Meindl A, Menon U, Nevanlinna H, Newman WG, Nodora J, Offit K, Olsson H, Orr N, Park-Simon TW, Patel A, Peto J, Pita G, Plaseska-Karanfilska D, Prentice R, Punie K, Pylkas K, Radice P, Rennert G, Romero A, Ruediger T, Saloustros E, Sampson S, Sandler DP, Sawyer EJ, Schmutzler RK, Schoemaker MJ, Schottker B, Sherman ME, Shu XO, Smichkoska S, Southey MC, Spinelli JJ, Swerdlow AJ, Tamimi RM, Tapper WJ, Taylor JA, Teras LR, Terry MB, Torres D, Troester MA, Vachon CM, Van Deurzen CHM, Van Veen EM, Wagner P, Weinberg CR, Wendt C, Wesseling J, Winqvist R, Wolk A, Yang XR, Zheng W, Couch FJ, Simard J, Kraft P, Easton DF, Pharoah PDP, Schmidt MK, Garcia-Closas M, Chatterjee N (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 24

Journal Issue: 1

DOI: 10.1186/s13058-021-01484-x

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.

Authors with CRIS profile

Involved external institutions

QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) University of Cambridge United Kingdom (GB) British Columbia Cancer Agency Canada (CA) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Sydney (USYD) Australia (AU) Servizo Galego de Saúde Spain (ES) University of Sheffield United Kingdom (GB) Cyprus Institute of Neurology and Genetics Cyprus (CY) Cancer Council Victoria Australia (AU) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) National Cancer Institute (NCI) United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University of Utah United States (USA) (US) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) Erasmus University Medical Center (MC) Netherlands (NL) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Lund University / Lunds universitet Sweden (SE) Oulun Yliopisto / University of Oulo Finland (FI) Mount Sinai Hospital (MSH) Canada (CA) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) Karolinska Institute Sweden (SE) University of Southampton United Kingdom (GB) Fox Chase Cancer Center United States (USA) (US) Hospital Universitario Puerta de Hierro - Majadahonda Spain (ES) Evangelisches Krankenhaus Oberhausen Germany (DE) University of Eastern Finland Finland (FI) The Institute of Cancer Research (ICR) United Kingdom (GB) Ludwig-Maximilians-Universität (LMU) Germany (DE) American Cancer Society United States (USA) (US) Manchester University NHS Foundation Trust (MFT) United Kingdom (GB) University of Edinburgh United Kingdom (GB) Södersjukhuset Sweden (SE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of Southern California (USC) United States (USA) (US) McGill University Canada (CA) Cyprus School of Molecular Medicine (CSMM) Cyprus (CY) The Alfred Hospital Australia (AU) University of Manchester United Kingdom (GB) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) Central University Hospital of Asturias Spain (ES) Queen's University United Kingdom (GB) University of Oslo Norway (NO) Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI / NKI-AVL) Netherlands (NL) École Polytechnique - Université Paris-Saclay France (FR) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Robert-Bosch-Krankenhaus Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Université Laval (UL) Canada (CA) Mayo Clinic United States (USA) (US) Columbia University United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) Harvard University United States (USA) (US) Städtisches Klinikum Karlsruhe Germany (DE) Vanderbilt University United States (USA) (US) King’s College London United Kingdom (GB) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Fred Hutchinson Cancer Research Center United States (USA) (US) National Institute of Environmental Health Sciences (NIEHS) United States (USA) (US) Johns Hopkins University (JHU) United States (USA) (US) General University Hospital of Larissa Greece (GR) Cornell University United States (USA) (US) University College London (UCL) United Kingdom (GB) Stanford University United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Hospital Clínico San Carlos Spain (ES) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Universität zu Köln Germany (DE) University of Westminster United Kingdom (GB) Saints Cyril and Methodius University of Skopje / Универзитет „Св. Кирил и Методиј“ во Скопје Republic of North Macedonia (MK) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung, Institut der Ruhr-Universität Bochum (IPA) Germany (DE) BC Cancer Canada (CA) Carmel Medical Center Israel (IL) University of Copenhagen Denmark (DK) Acibadem Sistina Hospital Republic of North Macedonia (MK) Leiden University Medical Center Netherlands (NL) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) The University of Melbourne Australia (AU) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) London School of Hygiene and Tropical Medicine United Kingdom (GB) University of California Irvine United States (USA) (US)

How to cite

APA:

Ahearn, T.U., Zhang, H., Michailidou, K., Milne, R.L., Bolla, M.K., Dennis, J.,... Chatterjee, N. (2022). Common variants in breast cancer risk loci predispose to distinct tumor subtypes. Breast Cancer Research, 24(1). https://doi.org/10.1186/s13058-021-01484-x

MLA:

Ahearn, Thomas U., et al. "Common variants in breast cancer risk loci predispose to distinct tumor subtypes." Breast Cancer Research 24.1 (2022).

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