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Body Mass Index and Breast Cancer Survival: A Mendelian Randomisation Analysis

Accepted version
Peer-reviewed

Change log

Authors

Guo, Q 
et al 

Abstract

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 randomisation 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 (2,475 events) of European ancestry. We created 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 (HR=1.11, per one-unit increment of GRS, 95% 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).

Conclusion: 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.

Description

Keywords

body mass index, breast cancer survival, mendelian randomisation, epidemiology, genetics

Journal Title

International Journal of Epidemiology

Conference Name

Journal ISSN

0300-5771
1464-3685

Volume Title

46

Publisher

Oxford University Press
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (60098573)
Cancer Research UK (unknown)
Cancer Research UK (CB4140)
Cancer Research Uk (None)
Addenbrooke's Charitable Trust (ACT) (KDD/9776)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
Cancer Research Uk (None)
Cancer Research Uk (None)
Breast Cancer Now (None)
Medical Research Council (MR/L003120/1)
Wellcome Trust (100114/Z/12/Z)
Cancer Research UK (12014)
Cancer Research UK (10118)
British Heart Foundation (None)
Medical Research Council (MC_UU_00002/7)
Wellcome Trust (204623/Z/16/Z)
The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). The Breast Cancer Association Consortium (BCAC) is funded by Cancer Research-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). ELAN Program of the University Hospital Erlangen (BBCC). Funds from Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5x1000” ). D.F.E is a Principal Research Fellow of Cancer Research UK. J.L.H is a National Health and Medical Research Council (NHMRC) Australia Fellow. S.B is supported by a fellowship from the Wellcome Trust (100114). M.C.S. is a NHMRC Senior Research Fellow. G.C.T is an NHMRC Senior Principal Research Fellow. D.L is supported by the FWO and the KULPFV/10/016-SymBioSysII. J.L is a UNESCO-L'Oréal International Fellow. I.L.A. holds the Anne and Max Tanenbaum Chair in Molecular Medicine at Mount Sinai Hospital and the University of Toronto. K.A.P. is an Australian National Breast Cancer Foundation Practitioner Fellow. Further funding details are in the attached Supporting information.