Mendelian randomization analyses of associations between breast cancer and bone mineral density

The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian r...

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Bibliographic Details
Published in:Scientific reports 2023-01, Vol.13 (1), p.1721-1721, Article 1721
Main Authors: Wu, Hong, Wang, Hui, Liu, Di, Liu, Zhibing, Zhang, Weiming
Format: Article
Language:English
Subjects:
631/67
631/67/69
Bone cancer
Bone density
Bone Density - genetics
Bone mineral density
Breast cancer
Genome-wide association studies
Genome-Wide Association Study
Genomes
Humanities and Social Sciences
Mendelian Randomization Analysis
multidisciplinary
Neoplasms
Risk factors
Science
Science (multidisciplinary)
Statistical analysis
Testosterone
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Summary:The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10 −4 ) as might its ER+ subtype (FDR = 1.51 × 10 −4 ). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10 −6 ). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10 −3 ) as could total testosterone (TT) (FDR = 5.81 × 10 −3 ). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10 −6 ) as could TT (FDR = 5.55 × 10 −4 ). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-28899-0