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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 publication

DOI

10.1093/ije/dyx131

Type

Journal article

Journal

Int J Epidemiol

Publication Date

01/12/2017

Volume

46

Pages

1814 - 1822

Keywords

Body mass index, Mendelian randomization, breast cancer survival, epidemiology, genetics, Body Mass Index, Breast Neoplasms, Causality, Europe, European Continental Ancestry Group, Female, Genetic Variation, Humans, Mendelian Randomization Analysis, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Assessment, Risk Factors, Survival Analysis