Key result
Genetically predicted higher levels of IGF-I were associated with an increased risk of overall breast cancer (OR 1.10), while IGFBP-3 was associated with postmenopausal breast cancer.
Why the study?
Circulating lipids are associated with breast cancer, which may partly reflect an effect of lipids on insulin-like growth factors.
Do genetically predicted circulating lipids and IGFs affect the risk of breast cancer?
Observational
Do genetically predicted circulating lipids and IGFs affect the risk of breast cancer?
Odds Ratio: 1.1 (95% CI 1.02–1.18)
p-value: p=0.01
Genetically predicted LDL-C and triglycerides may influence breast cancer risk through alterations in the IGF axis, though multivariable MR instruments were weak.
Adds genetic support for IGF-I in breast cancer etiology; hypothesis-generating and should not yet alter clinical risk assessment.
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.
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Tan et al. (2020) conducted an observational in Breast cancer. Genetically predicted IGF-I vs. Lower genetically predicted IGF-I was evaluated on Overall breast cancer risk (OR 1.10, 95% CI 1.02-1.18, p=0.01). Genetically predicted higher levels of IGF-I were associated with an increased risk of overall breast cancer (OR 1.10), while IGFBP-3 was associated with postmenopausal breast cancer.
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