Yang Yanjiang, Chen Min, Yang Wenwen
Department of Rheumatology and Immunology, The People's Hospital of Qiandongnan Autonomous Prefecture, Kaili, Guizhou, China.
The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Front Oncol. 2024 Nov 21;14:1449956. doi: 10.3389/fonc.2024.1449956. eCollection 2024.
Observational investigations have indicated a notable correlation between body mass index (BMI) and breast cancer (BC). Nevertheless, the precise biological pathways driving this correlation remain ambiguous. Consequently, we utilized Mendelian randomization (MR) techniques to explore the causative link between BMI and genetic predisposition to BC, as well as the potential intermediary influences.
Utilizing extensive cohorts sourced from publicly accessible genome-wide association studies (GWAS) datasets of European populations, we conducted Mendelian randomization (MR) analysis. The primary method employed was the Inverse Variance Weighted (IVW) model. We evaluated both heterogeneity and horizontal pleiotropy. Our MR analysis unveiled several metabolites and sex hormones as mediators in the association between BMI and BC.
The IVW model indicated significant negative causal correlations between BMI and BC, ERBC, and ERBC. Thirty-five metabolites, thirty-three metabolites and sex hormones, and fifteen metabolites respectively mediated the causal effects of BMI on BC, ER+BC, and ERBC. Furthermore, our study found that BMI influences BC risk through different mediating factors; BMI increases ER+BC risk through the pathway of sex hormones (biologically available testosterone) and decreases the causal relationship of BC risk through multiple metabolite pathways.
This study discovered that BMI increases ERBC risk through the pathway of sex hormones (biologically available testosterone), and decreases BC risk through multiple metabolite pathways causally. These discoveries could offer insights into the development of preventive strategies and interventions for BC, while further investigations should delve into alternative feasible biological pathways.
观察性研究表明体重指数（BMI）与乳腺癌（BC）之间存在显著相关性。然而，驱动这种相关性的确切生物学途径仍不明确。因此，我们利用孟德尔随机化（MR）技术来探索BMI与BC遗传易感性之间的因果关系，以及潜在的中介影响。
利用来自欧洲人群公开可用的全基因组关联研究（GWAS）数据集的大量队列，我们进行了孟德尔随机化（MR）分析。采用的主要方法是逆方差加权（IVW）模型。我们评估了异质性和水平多效性。我们的MR分析揭示了几种代谢物和性激素作为BMI与BC之间关联的中介。
IVW模型表明BMI与BC、雌激素受体阳性乳腺癌（ER+BC）和雌激素受体阴性乳腺癌（ER-BC）之间存在显著的负因果相关性。35种代谢物、33种代谢物和性激素以及15种代谢物分别介导了BMI对BC、ER+BC和ER-BC的因果效应。此外，我们的研究发现BMI通过不同的中介因素影响BC风险；BMI通过性激素（生物可利用睾酮）途径增加ER+BC风险，并通过多种代谢物途径降低BC风险的因果关系。
本研究发现BMI通过性激素（生物可利用睾酮）途径增加ER-BC风险，并通过多种代谢物途径因果性地降低BC风险。这些发现可为BC预防策略和干预措施的制定提供见解，而进一步的研究应深入探讨其他可行的生物学途径。
