Body mass index and breast cancer survival: a Mendelian randomization analysis.
Qi Guo,
Stephen Burgess,
Constance Turman,
Manjeet K Bolla,
Qin Wang,
Michael Lush,
Jean Abraham,
Kristiina Aittomäki,
Irene L Andrulis,
Carmel Apicella,
Volker Arndt,
Myrto Barrdahl,
Javier Benitez,
Christine D Berg,
Carl Blomqvist,
Stig E Bojesen,
Bernardo Bonanni,
Judith S Brand,
Hermann Brenner,
Annegien Broeks,
Barbara Burwinkel,
Carlos Caldas,
Daniele Campa,
Federico Canzian,
Jenny Chang-Claude,
Stephen J Chanock,
Suet-Feung Chin,
Fergus J Couch,
Angela Cox,
Simon S Cross,
Cezary Cybulski,
Kamila Czene,
Hatef Darabi,
Peter Devilee,
W Ryan Diver,
Alison M Dunning,
Helena M Earl,
Diana M Eccles,
Arif B Ekici,
Mikael Eriksson,
D Gareth Evans,
Peter A Fasching,
Jonine Figueroa,
Dieter Flesch-Janys,
Henrik Flyger,
Susan M Gapstur,
Mia M Gaudet,
Graham G Giles,
Gord Glendon,
Mervi Grip,
Jacek Gronwald,
Lothar Haeberle,
Christopher A Haiman,
Per Hall,
Ute Hamann,
Susan Hankinson,
Jaana M Hartikainen,
Alexander Hein,
Louise Hiller,
Frans B Hogervorst,
Bernd Holleczek,
Maartje J Hooning,
Robert N Hoover,
Keith Humphreys,
David J Hunter,
Anika Hüsing,
Anna Jakubowska,
Arja Jukkola-Vuorinen,
Rudolf Kaaks,
Maria Kabisch,
Vesa Kataja,
,
Julia A Knight,
Linetta B Koppert,
Veli-Matti Kosma,
Vessela N Kristensen,
Diether Lambrechts,
Loic Le Marchand,
Jingmei Li,
Annika Lindblom,
Sara Lindström,
Jolanta Lissowska,
Jan Lubinski,
Mitchell J Machiela,
Arto Mannermaa,
Siranoush Manoukian,
Sara Margolin,
Federik Marme,
John W M Martens,
Catriona McLean,
Primitiva Menéndez,
Roger L Milne,
Anna Marie Mulligan,
Taru A Muranen,
Heli Nevanlinna,
Patrick Neven,
Sune F Nielsen,
Børge G Nordestgaard,
Janet E Olson,
Jose I A Perez,
Paolo Peterlongo,
Kelly-Anne Phillips,
Christopher J Poole,
Katri Pylkäs,
Paolo Radice,
Nazneen Rahman,
Thomas Rüdiger,
Anja Rudolph,
Elinor J Sawyer,
Fredrick Schumacher,
Petra Seibold,
Caroline Seynaeve,
Mitul Shah,
Ann Smeets,
Melissa C Southey,
Rob A E M Tollenaar,
Ian Tomlinson,
Helen Tsimiklis,
Hans-Ulrich Ulmer,
Celine Vachon,
Ans M W van den Ouweland,
Laura J Van't Veer,
Hans Wildiers,
Walter Willett,
Robert Winqvist,
M Pilar Zamora,
Georgia Chenevix-Trench,
Thilo Dörk,
Douglas F Easton,
Montserrat García-Closas,
Peter Kraft,
John L Hopper,
Wei Zheng,
Marjanka K Schmidt,
Paul D P Pharoah
Abstract
METHODS
We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.
CONCLUSIONS
Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
RESULTS
BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).
BACKGROUND
There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.