Estimating the effect of lipids on IGF axis and subsequent breast cancer risk

Vanessa Y. Tan, Caroline J. Bull, Kalina M. Biernacka, Alexander Teumer, Laura Corbin, Tom Dudding, Eleanor Sanderson, Qibin Qi, Robert C. Kaplan, Jerome I. Rotter, Nele Friedrich, Uwe Völker, Julia Mayerle, Claire M. Perks, Jeff M.P. Holly, Nicholas J. Timpson

Research output: Contribution to journalArticlepeer-review


Circulating lipids have been associated with breast cancer (BCa). This association may, in part, be due to an effect of lipids on insulin-like growth factors (IGFs), which have been reliably associated with BCa. In two-sample Mendelian randomization (MR) analyses, we found that low density lipoprotein (LDL-C) was associated with IGFBP-3 (beta:0.08 SD; 95%CI:0.02,0.15; p=0.01, per SD increase in LDL-C) and IGFBP-3 was associated with postmenopausal BCa (OR:1.09; 95%CI:1.00,1.19;p=0.05, per SD increase in IGFBP-3). We also found that triglycerides were associated with IGF-I (beta:-0.13SD; 95%CI:-0.22,-0.03, per SD increase in triglycerides) and that IGF-I was associated with overall BCa (OR:1.10;95%CI:1.02,1.18, per SD increase in IGF-I). Taken together, these results suggest that IGFBP-3 may be a potential causal step between LDL-C and postmenopausal BCa and IGF-I a potential causal for triglycerides. Our two-step MR results build on evidence linking circulating lipids and IGFs with BCa, however, multivariable MR analyses are currently unable to support this relationship due to weak instruments.

Original languageEnglish (US)
JournalUnknown Journal
StatePublished - Jun 7 2020


  • Breast cancer
  • Insulin-like growth factors
  • Lipids
  • Mendelian randomization

ASJC Scopus subject areas

  • Medicine(all)

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