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Research Paper|Volume 16, Issue 15|pp 11626—11655

Causal role of blood metabolites in HER-positive and HER-negative breast cancer: a Mendelian randomization (MR) study

Jian Yue1,2,3, Huiying Fang4, Sheng Chen3, Lei Gu5, Guosheng Ren1,2
  • 1Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 3Department of Breast Surgery, Gaozhou People’s Hospital, Gaozhou, China
  • 4Department of Breast Cancer Center, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing University Cancer Hospital, Chongqing, China
  • 5Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China
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Received: January 16, 2024Accepted: July 5, 2024Published: August 2, 2024
https://doi.org/10.18632/aging.206042

Copyright: © 2024 Yue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Previous studies provide evidence that in vivo metabolites are associated with breast cancer (BC). However, the causal relationship between blood metabolites and BC remains unclear.

Method: Comprehensive two-sample Mendelian randomization analysis was conducted to determine the causal association between 1400 publicly available genetic data on metabolic factors and human epidermal growth factor receptor positive (HER+) BC or HER- BC in this study.

Result: Epiandrosterone sulfate levels (OR = 1.07, 95% CI = 1.02 ~ 1.10, p = 0.0013), 5alpha-androstan-3beta,17beta-diol monosulfate (2) levels (OR = 1.07, 95% CI = 1.03 ~ 1.12, p = 0.0012), glycohyocholate levels (OR = 0.85, 95% CI = 0.77 ~ 0.93, p = 0.0007) and etiocholanolone glucuronide levels (OR = 1.12, 95% CI = 1.05 ~ 1.20, p = 0.0013) were causally correlated with HER+ BC. 5 metabolites were causally correlated with HER- BC: Vanillic acid glycine levels (OR = 1.14, 95% CI = 1.06 ~ 1.22, p = 0.0003), Thyroxine levels (OR = 1.26, 95% CI = 1.11 ~ 1.44, p = 0.0004), 1-palmitoyl-2-linoleoyl-GPI (16:0/18:2) levels (OR = 0.86, 95% CI = 0.79 ~ 0.94, p = 0.0010), N-acetylphenylalanine levels (OR = 1.12, 95% CI = 1.05 ~ 1.19, p = 0.0007) and Glucose-to-mannose ratio (OR = 1.15, 95% CI = 1.06 ~ 1.24, p = 0.0008). Two common causally related metabolites were identified: Gamma-glutamyl glutamate and X-12849 levels.

Conclusions: Our study has respectively demonstrated the connection between blood metabolites and HER+ or HER- BC by genetic means, thereby offering opportunities for therapeutic targets.