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

Ben Zhang(University of Copenhagen), Xiao‐Ou Shu(University of Copenhagen), Ryan Delahanty(University of Copenhagen), Chenjie Zeng(University of Copenhagen), Kyriaki Michailidou(University of Copenhagen), Manjeet K. Bolla(University of Copenhagen), Qin Wang(University of Copenhagen), Joe Dennis(University of Copenhagen), Wanqing Wen(University of Copenhagen), Jirong Long(University of Copenhagen), Chun Li(University of Copenhagen), Alison M. Dunning(University of Copenhagen), Jenny Chang‐Claude(University of Copenhagen), Mitul Shah(University of Copenhagen), Barbara Perkins(University of Copenhagen), Kamila Czene(University of Copenhagen), Hatef Darabi(University of Copenhagen), Mikael Eriksson(University of Copenhagen), Stig E. Bojesen(University of Copenhagen), Børge G. Nordestgaard(University of Copenhagen), Sune F. Nielsen(University of Copenhagen), Henrik Flyger(University of Copenhagen), Diether Lambrechts(University of Copenhagen), Patrick Neven(University of Copenhagen), Hans Wildiers(University of Copenhagen), Giuseppe Floris(University of Copenhagen), Marjanka K. Schmidt(University of Copenhagen), Matti A. Rookus(University of Copenhagen), Katja van den Hurk(University of Copenhagen), Wim de Kort(University of Copenhagen), Fergus J. Couch(University of Copenhagen), Janet E. Olson(University of Copenhagen), Emily Hallberg(University of Copenhagen), Celine M. Vachon(University of Copenhagen), Anja Rudolph(University of Copenhagen), Petra Seibold(University of Copenhagen), Dieter Flesch‐Janys(University of Copenhagen), Julian Peto(University of Copenhagen), Isabel dos‐Santos‐Silva(University of Copenhagen), Olivia Fletcher(University of Copenhagen), Nichola Johnson(University of Copenhagen), Heli Nevanlinna(University of Copenhagen), Taru Muranen(University of Copenhagen), Kristiina Aittomäki(University of Copenhagen), Carl Blomqvist(University of Copenhagen), Jingmei Li(University of Copenhagen), Keith Humphreys(University of Copenhagen), Judith S. Brand(University of Copenhagen), Pascal Guénel(University of Copenhagen), Thérèse Truong(University of Copenhagen), Emilie Cordina‐Duverger(University of Copenhagen), F. Ménégaux(University of Copenhagen), Barbara Burwinkel(University of Copenhagen), Frederik Marmé(University of Copenhagen), Rongxi Yang(University of Copenhagen), Harald Surowy(University of Copenhagen), Javier Benı́tez(University of Copenhagen), M. Pilar Zamora(University of Copenhagen), José Ignacio Arias Pérez(University of Copenhagen), Angela Cox(University of Copenhagen), Simon S. Cross(University of Copenhagen), Malcolm Reed(University of Copenhagen), Irene L. Andrulis(University of Copenhagen), Julia A. Knight(University of Copenhagen), Gord Glendon(University of Copenhagen), Sandrine Tchatchou(University of Copenhagen), Elinor J. Sawyer(University of Copenhagen), Ian Tomlinson(University of Copenhagen), Michael J. Kerin(University of Copenhagen), Nicola Miller(University of Copenhagen), Georgia Chenevix‐Trench(University of Copenhagen), kConFab Investigators, Australian Ovarian Study Group(University of Copenhagen), Christopher A. Haiman(University of Copenhagen), Brian E. Henderson(University of Copenhagen), Fredrick R. Schumacher(University of Copenhagen), Loı̈c Le Marchand(University of Copenhagen), Annika Lindblom(University of Copenhagen), Sara Margolin(University of Copenhagen), Maartje J. Hooning(University of Copenhagen), John W.M. Martens(University of Copenhagen), Madeleine M.A. Tilanus‐Linthorst(University of Copenhagen), J. Margriet Collée(University of Copenhagen), John L. Hopper(University of Copenhagen), Melissa C. Southey(University of Copenhagen), Helen Tsimiklis(University of Copenhagen), Carmel Apicella(University of Copenhagen), Susan Slager(University of Copenhagen), Amanda E. Toland(University of Copenhagen), Christine B. Ambrosone(University of Copenhagen), Drakoulis Yannoukakos(University of Copenhagen), Graham G. Giles(University of Copenhagen), Roger L. Milne(University of Copenhagen), Catriona McLean(University of Copenhagen), Peter A. Fasching(University of Copenhagen), Lothar Haeberle(University of Copenhagen), Arif B. Ekici(University of Copenhagen), Matthias W. Beckmann(University of Copenhagen), Hermann Brenner(University of Copenhagen), Aida Karina Dieffenbach(University of Copenhagen), Volker Arndt(University of Copenhagen), Christa Stegmaier(University of Copenhagen), Anthony J. Swerdlow(University of Copenhagen), Alan Ashworth(University of Copenhagen), Nick Orr(University of Copenhagen), Michael E. Jones(University of Copenhagen), Jonine D. Figueroa(University of Copenhagen), Montserrat García‐Closas(University of Copenhagen), Louise A. Brinton(University of Copenhagen), Jolanta Lissowska(University of Copenhagen), Martine Dumont(University of Copenhagen), Robert Winqvist(University of Copenhagen), Katri Pylkäs(University of Copenhagen), Arja Jukkola‐Vuorinen(University of Copenhagen), Mervi Grip(University of Copenhagen), Hiltrud Brauch(University of Copenhagen), Thomas Brüning(University of Copenhagen), Yon-Dschun Ko(University of Copenhagen), Paolo Peterlongo(University of Copenhagen), Siranoush Manoukian(University of Copenhagen), Bernardo Bonanni(University of Copenhagen), Paolo Radice(University of Copenhagen), Natalia Bogdanova(University of Copenhagen), Natalia Antonenkova(University of Copenhagen), Thilo Dörk(University of Copenhagen), Arto Mannermaa(University of Copenhagen), Vesa Kataja(University of Copenhagen), Veli‐Matti Kosma(University of Copenhagen), Jaana M. Hartikainen(University of Copenhagen), Peter Devilee(University of Copenhagen), Caroline Seynaeve(University of Copenhagen), Christi J. van Asperen(University of Copenhagen), Anna Jakubowska(University of Copenhagen), Jan Lubiński(University of Copenhagen), Katarzyna Jaworska–Bieniek(University of Copenhagen), Katarzyna Durda(University of Copenhagen), Ute Hamann(University of Copenhagen), Diana Torres(University of Copenhagen), Rita K. Schmutzler(University of Copenhagen), Susan L. Neuhausen(University of Copenhagen), Hoda Anton‐Culver(University of Copenhagen), Vessela N. Kristensen(University of Copenhagen), Grethe I.G. Alnæs(University of Copenhagen), the DRIVE Project(University of Copenhagen), Brandon L. Pierce(University of Copenhagen), Peter Kraft(University of Copenhagen), Ulrike Peters(University of Copenhagen), Sara Lindström(University of Copenhagen), Daniela Seminara(University of Copenhagen), Stephen Burgess(University of Copenhagen), Habibul Ahsan(University of Copenhagen), Alice S. Whittemore(University of Copenhagen), Esther M. John(University of Copenhagen), Marilie D. Gammon(University of Copenhagen), Kathleen E. Malone(University of Copenhagen), Daniel C. Tessier(University of Copenhagen), Daniel Vincent(University of Copenhagen), François Bacot(University of Copenhagen), Craig Luccarini(University of Copenhagen), Caroline Baynes(University of Copenhagen), Shahana Ahmed(University of Copenhagen), Mel Maranian(University of Copenhagen), Catherine S. Healey(University of Copenhagen), Anna González‐Neira(University of Copenhagen), Guillermo Pita(University of Copenhagen), M. Rosario Alonso(University of Copenhagen), Núria Álvarez(University of Copenhagen), Daniel Herrero(University of Copenhagen), Paul D.P. Pharoah(University of Copenhagen), Jacques Simard(University of Copenhagen), Per Hall(University of Copenhagen), David J. Hunter(University of Copenhagen), Douglas F. Easton(Vanderbilt University), Wei Zheng(Vanderbilt University)
JNCI Journal of the National Cancer Institute
August 20, 2015
10.1093/jnci/djv219
Cited by 146Open Access
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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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