Why Was This Study Done?
• Body mass index (BMI) has been linked to breast cancer risk in conventional population studies.
• In these studies, high BMI is associated with reduced risk of breast cancer in premenopausal women but with increased risk in postmenopausal women. These changed risks may be caused by BMI or caused by environmental factors that are associated with BMI.
• We sought to use a research tool from the genetics field to understand BMI’s causal role in breast cancer.

What Did the Researchers Do and Find?
• We took advantage of previously identified genetic sequence variations that are associated with BMI in European populations and used these variants to predict BMI. These variants are set at birth and are not affected by environmental factors; thus, outcomes associated with high BMI as predicted by genetic variants are more likely to be caused by high BMI itself rather than by environmental factors that are associated with high BMI.
• Using databases containing individual genetic sequences and breast cancer diagnoses in a European population, we tested whether genetically predicted BMI was associated with diagnosis of breast cancer in either pre- or postmenopausal women.
• We found that genetically predicted high BMI was associated with decreased breast cancer risk, in both cancer databases. Unexpectedly, this was true for both pre- and postmenopausal women.

What Do These Findings Mean?
• Our results from postmenopausal women contradict prior findings from population studies, which used measured, rather than genetically predicted, BMI.
• BMI predicted using genetic variants identified to date may be more closely related to body weight in early life or midlife, which is negatively associated with risk of breast cancer. Measured high BMI later in life may be influenced by environmental factors that are associated with increased risk of breast cancer.
• More research is needed on the interrelationship of genetic factors, environment, and BMI in the risk of breast cancer.

doi.org/10.1371/journal.pmed.1002105, hdl.handle.net/1765/93503
PLoS Medicine
Department of Surgery

Guo, Y., Warren Andersen, S., Shu, X.-O., Michailidou, K., Bolla, M. K., Wang, Q., … Zheng, W. (2016). Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent. PLoS Medicine, 13(8). doi:10.1371/journal.pmed.1002105