A causal relationship between bone mineral density and breast cancer risk: a mendelian randomization study based on east Asian population

Autor: Ziyang Cheng, Hui Xu, Xin Wang, Tao Teng, Bin Li, Zhong Cao, Zhichao Li, Jiayi Zhang, Jin Xuan, Fengyi Zhang, Yaxin Chen, Yujie Li, Wenbo Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Cancer, Vol 24, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 1471-2407
DOI: 10.1186/s12885-024-12908-0
Popis: Abstract Background Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). Methods Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran’s Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. Results The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ( $$\:OR\:=\:1.22$$ , $$\:95\%\:CI:\:1.13-1.33$$ , $$\:P
Databáze: Directory of Open Access Journals
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