Body mass index and breast cancer survival: a Mendelian randomization analysis

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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 & 114 others 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, 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, kConFab/AOCS Investigators, 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 WM 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 IA 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 MW 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 DP Pharoah

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.

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.

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).

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.

Original languageEnglish
JournalInternational Journal of Epidemiology
Volume46
Issue number6
Pages (from-to)1814-1822
ISSN0300-5771
DOIs
Publication statusPublished - 2017

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