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.

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Keywords Body mass index, Breast cancer survival, Epidemiology, Genetics, Mendelian randomization
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Journal International Journal of Epidemiology
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Guo, Q, Burgess, S, Turman, C. (Constance), Bolla, M.K. (Manjeet K.), Wang, Q. (Qin), Lush, M. (Michael), … Pharoah, P.D.P. (2017). Body mass index and breast cancer survival. International Journal of Epidemiology, 46(6), 1891–1902. doi:10.1093/ije/dyx131