TY - JOUR
T1 - Estimating the effect of lipids on IGF axis and subsequent breast cancer risk
AU - Tan, Vanessa Y.
AU - Bull, Caroline J.
AU - Biernacka, Kalina M.
AU - Teumer, Alexander
AU - Corbin, Laura
AU - Dudding, Tom
AU - Sanderson, Eleanor
AU - Qi, Qibin
AU - Kaplan, Robert C.
AU - Rotter, Jerome I.
AU - Friedrich, Nele
AU - Völker, Uwe
AU - Mayerle, Julia
AU - Perks, Claire M.
AU - Holly, Jeff M.P.
AU - Timpson, Nicholas J.
N1 - Publisher Copyright:
The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/6/7
Y1 - 2020/6/7
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Insulin-like growth factors
KW - Lipids
KW - Mendelian randomization
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U2 - 10.1101/2020.06.04.20122630
DO - 10.1101/2020.06.04.20122630
M3 - Article
AN - SCOPUS:85099248707
JO - Journal of Trace Elements in Medicine and Biology
JF - Journal of Trace Elements in Medicine and Biology
SN - 0946-672X
ER -