Body mass index and breast cancer survival: A Mendelian randomization analysis

kConFab/AOCS Investigators

Research output: Contribution to journalArticle

10 Scopus citations

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 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 languageEnglish (US)
Pages (from-to)1891-1902
Number of pages12
JournalInternational journal of epidemiology
Volume46
Issue number6
DOIs
StatePublished - Dec 1 2017

Keywords

  • Body mass index
  • Breast cancer survival
  • Epidemiology
  • Genetics
  • Mendelian randomization

ASJC Scopus subject areas

  • Epidemiology

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