Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.
;
Isabel
Dos-Santos-Silva
;
Olivia
Fletcher
;
Nichola
Johnson
;
Heli
Nevanlinna
;
Taru A
Muranen
;
Kristiina
Aittomäki
;
Carl
Blomqvist
;
Jingmei
Li
;
Keith
Humphreys
;
Judith
Brand
;
Pascal
Guénel
;
Thérèse
Truong
;
Emilie
Cordina-Duverger
;
Florence
Menegaux
;
Barbara
Burwinkel
;
Frederik
Marme
;
Rongxi
Yang
;
Harald
Surowy
;
Javier
Benitez
;
M Pilar
Zamora
;
Jose IA
Perez
;
Angela
Cox
;
Simon S
Cross
;
Malcolm WR
Reed
;
Irene L
Andrulis
;
Julia A
Knight
;
Gord
Glendon
;
Sandrine
Tchatchou
;
Elinor J
Sawyer
;
Ian
Tomlinson
;
Michael J
Kerin
;
Nicola
Miller
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Georgia
Chenevix-Trench
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kConFab Investigators, Australian Ovarian Study Group
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Christopher A
Haiman
;
Brian E
Henderson
;
Fredrick
Schumacher
;
Loic Le
Marchand
;
Annika
Lindblom
;
Sara
Margolin
;
Maartje J
Hooning
;
John WM
Martens
;
Madeleine MA
Tilanus-Linthorst
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J Margriet
Collée
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John L
Hopper
;
Melissa C
Southey
;
Helen
Tsimiklis
;
Carmel
Apicella
;
Susan
Slager
;
Amanda E
Toland
;
Christine B
Ambrosone
;
Drakoulis
Yannoukakos
;
Graham G
Giles
;
Roger L
Milne
;
Catriona
McLean
;
Peter A
Fasching
;
Lothar
Haeberle
;
Arif B
Ekici
;
Matthias W
Beckmann
;
Hermann
Brenner
;
Aida Karina
Dieffenbach
;
Volker
Arndt
;
Christa
Stegmaier
;
Anthony J
Swerdlow
;
Alan
Ashworth
;
Nick
Orr
;
Michael
Jones
;
Jonine
Figueroa
;
Montserrat
Garcia-Closas
;
Louise
Brinton
;
Jolanta
Lissowska
;
Martine
Dumont
;
Robert
Winqvist
;
Katri
Pylkäs
;
Arja
Jukkola-Vuorinen
;
Mervi
Grip
;
Hiltrud
Brauch
;
Thomas
Brüning
;
Yon-Dschun
Ko
;
Paolo
Peterlongo
;
Siranoush
Manoukian
;
Bernardo
Bonanni
;
Paolo
Radice
;
Natalia
Bogdanova
;
Natalia
Antonenkova
;
Thilo
Dörk
;
Arto
Mannermaa
;
Vesa
Kataja
;
Veli-Matti
Kosma
;
Jaana M
Hartikainen
;
Peter
Devilee
;
Caroline
Seynaeve
;
Christi J
Van Asperen
;
Anna
Jakubowska
;
Jan
Lubiński
;
Katarzyna
Jaworska-Bieniek
;
Katarzyna
Durda
;
Ute
Hamann
;
Diana
Torres
;
Rita K
Schmutzler
;
Susan L
Neuhausen
;
Hoda
Anton-Culver
;
Vessela N
Kristensen
;
Grethe I
Grenaker Alnæs
;
DRIVE Project
;
Brandon L
Pierce
;
Peter
Kraft
;
Ulrike
Peters
;
Sara
Lindstrom
;
Daniela
Seminara
;
Stephen
Burgess
;
Habibul
Ahsan
;
Alice S
Whittemore
;
Esther M
John
;
Marilie D
Gammon
;
Kathleen E
Malone
;
Daniel C
Tessier
;
Daniel
Vincent
;
Francois
Bacot
;
Craig
Luccarini
;
Caroline
Baynes
;
Shahana
Ahmed
;
Mel
Maranian
;
Catherine S
Healey
;
Anna
González-Neira
;
Guillermo
Pita
;
M Rosario
Alonso
;
Nuria
Álvarez
;
Daniel
Herrero
;
Paul DP
Pharoah
;
Jacques
Simard
;
Per
Hall
;
David J
Hunter
;
Douglas F
Easton
;
Wei
Zheng
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(2015)
Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.
Journal of the National Cancer Institute, 107 (11).
djv219-djv219.
ISSN 0027-8874
DOI: 10.1093/jnci/djv219
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.