Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization

Zhang B, Shu XO, Delahanty RJ, Zeng C, Michailidou K, Bolla MK, Wang Q, Dennis J, Wen W, Long J, Li C, Dunning AM, Chang-Claude J, Shah M, Perkins BJ, Czene K, Darabi H, Eriksson M, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Lambrechts D, Neven P, Wildiers H, Floris G, Schmidt MK, Rookus MA, Van Den Hurk K, De Kort WLAM, Couch FJ, Olson JE, Hallberg E, Vachon C, Rudolph A, Seibold P, Flesch-Janys D, Peto J, Dos-Santos-Silva I, Fletcher O, Johnson N, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Li J, Humphreys K, Brand J, Guenel P, Truong T, Cordina-Duverger E, Menegaux F, Burwinkel B, Marme F, Yang R, Surowy H, Benitez J, Pilar Zamora M, Perez JIA, Cox A, Cross SS, Reed MWR, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Chenevix-Trench G, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Lindblom A, Margolin S, Hooning MJ, Martens JWM, Tilanus-Linthorst MMA, Collee JM, Hopper JL, Southey MC, Tsimiklis H, Apicella C, Slager S, Toland AE, Ambrosone CB, Yannoukakos D, Giles GG, Milne RL, Mclean C, Fasching P, Häberle L, Ekici AB, Beckmann M, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Swerdlow AJ, Ashworth A, Orr N, Jones M, Figueroa J, Garcia-Closas M, Brinton L, Lissowska J, Dumont M, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Brauch H, Bruening T, Ko YD, Peterlongo P, Manoukian S, Bonanni B, Radice P, Bogdanova N, Antonenkova N, Doerk T, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Devilee P, Seynaeve C, Van Asperen CJ, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Hamann U, Torres D, Schmutzler RK, Neuhausen SL, Anton-Culver H, Kristensen VN, Alnaes GIG, Pierce BL, Kraft P, Peters U, Lindstrom S, Seminara D, Burgess S, Ahsan H, Whittemore AS, John EM, Gammon MD, Malone KE, Tessier DC, Vincent D, Bacot F, Luccarini C, Baynes C, Ahmed S, Maranian M, Healey CS, Gonzalez-Neira A, Pita G, Rosario Alonso M, Alvarez N, Herrero D, Pharoah PDP, Simard J, Hall P, Hunter DJ, Easton DF, Zheng W (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 107

Journal Issue: 11

DOI: 10.1093/jnci/djv219

Abstract

Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear.We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients.The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5×10(-8).Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University Hospital Galway Ireland (IE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) University of Chicago United States (USA) (US) Harvard University United States (USA) (US) Fred Hutchinson Cancer Research Center Canada (CA) National Cancer Institute (NCI) United States (USA) (US) University of Cambridge United Kingdom (GB) Stanford University United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) McGill University Canada (CA) Centre hospitalier universitaire de Québec Canada (CA) Karolinska Institute Sweden (SE) Vanderbilt University United States (USA) (US) Herlev Hospital Denmark (DK) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Netherlands Cancer Institute (NKI) Netherlands (NL) Sanquin Netherlands (NL) Mayo Clinic United States (USA) (US) London School of Hygiene and Tropical Medicine United Kingdom (GB) Helsingin yliopisto / University of Helsinki Finland (FI) Genome Institute of Singapore Singapore (SG) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) Ruprecht-Karls-Universität Heidelberg Germany (DE) Hospital Monte Naranco Spain (ES) University of Sheffield United Kingdom (GB) University of Toronto Canada (CA) Hospital Universitario La Paz Spain (ES) King’s College London United Kingdom (GB) University of Oxford United Kingdom (GB) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Southern California (USC) United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Erasmus University Medical Center (MC) Netherlands (NL) The University of Melbourne Australia (AU) Ohio State University United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) The Alfred Hospital Australia (AU) Oulun Yliopisto / University of Oulo Finland (FI) Eberhard Karls Universität Tübingen Germany (DE) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) Germany (DE) Evangelische Kliniken Bonn gGmbH Germany (DE) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) Leiden University Netherlands (NL) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Universitätsklinikum Köln Germany (DE) City of Hope Medical Center United States (USA) (US) University of California Irvine United States (USA) (US)

How to cite

APA:

Zhang, B., Shu, X.-O., Delahanty, R.J., Zeng, C., Michailidou, K., Bolla, M.K.,... Zheng, W. (2015). Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization. Journal of the National Cancer Institute, 107(11). https://dx.doi.org/10.1093/jnci/djv219

MLA:

Zhang, Ben, et al. "Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization." Journal of the National Cancer Institute 107.11 (2015).

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