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Cancer Causes & Control
Published in: Cancer Causes & Control 2/2024

22-09-2023 | Breast Cancer | Original Paper

Untargeted serum metabolomic profiles and breast density in young women

Authors: Seungyoun Jung, Sarah Silva, Cher M. Dallal, Erin LeBlanc, Kenneth Paris, John Shepherd, Linda G. Snetselaar, Linda Van Horn, Yuji Zhang, Joanne F. Dorgan

Published in: Cancer Causes & Control | Issue 2/2024

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Abstract

Purpose of the study

Breast density is an established risk factor for breast cancer. However, little is known about metabolic influences on breast density phenotypes. We conducted untargeted serum metabolomics analyses to identify metabolic signatures associated with breast density phenotypes among young women.

Methods

In a cross-sectional study of 173 young women aged 25–29 who participated in the Dietary Intervention Study in Children 2006 Follow-up Study, 449 metabolites were measured in fasting serum samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable-adjusted mixed-effects linear regression identified metabolites associated with magnetic resonance imaging measured breast density phenotypes: percent dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute non-dense breast volume (ANDBV). Metabolite results were corrected for multiple comparisons using a false discovery rate adjusted p-value (q).

Results

The amino acids valine and leucine were significantly inversely associated with %DBV. For each 1 SD increase in valine and leucine, %DBV decreased by 20.9% (q = 0.02) and 18.4% (q = 0.04), respectively. ANDBV was significantly positively associated with 16 lipid and one amino acid metabolites, whereas no metabolites were associated with ADBV. Metabolite set enrichment analysis also revealed associations of distinct metabolic signatures with %DBV, ADBV, and ANDBV; branched chain amino acids had the strongest inverse association with %DBV (p = 0.002); whereas, diacylglycerols and phospholipids were positively associated with ANDBV (p ≤ 0.002), no significant associations were observed for ADBV.

Conclusion

Our results suggest an inverse association of branched chain amino acids with %DBV. Larger studies in diverse populations are needed.
Appendix
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Metadata
Title
Untargeted serum metabolomic profiles and breast density in young women
Authors
Seungyoun Jung
Sarah Silva
Cher M. Dallal
Erin LeBlanc
Kenneth Paris
John Shepherd
Linda G. Snetselaar
Linda Van Horn
Yuji Zhang
Joanne F. Dorgan
Publication date
22-09-2023
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 2/2024
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-023-01793-w

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