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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.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.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).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

International journal of epidemiology

Publication Date

12/2017

Volume

46

Pages

1814 - 1822

Addresses

Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Keywords

kConFab/AOCS Investigators, Humans, Breast Neoplasms, Receptors, Estrogen, Body Mass Index, Risk Assessment, Risk Factors, Survival Analysis, Causality, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Europe, Female, Meta-Analysis as Topic, Genetic Variation, Mendelian Randomization Analysis