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Background <p>The biological functions of mitochondria play a role in the occurrence and development of breast cancer, however, the causal relationship between them remains unclear.</p> Methods <p>Genetic instruments for mitochondrial biology and breast cancer were sourced from two genome-wide association studies (GWAS). Causal associations were assessed using Mendelian randomization analysis and validated through heterogeneity and sensitivity analyses. Additionally, the causal relationship between the identified mitochondrial proteins and the survival rate of breast cancer patients was further verified using the Kaplan-Meier Plotter.</p> Results <p>Analysis indicated causal associations between six mitochondrial proteins and breast cancer incidence. Inverse associations were found for ADP-ribose pyrophosphatase (ADPRase) and Cytochrome c oxidase subunit 8&#xa0;A (COX8A), while positive correlations were observed for Pyruvate carboxylase (PC), rRNA methyltransferase 3 (MRM3), Cytochrome c oxidase assembly factor 3 homolog (COA3), and Diablo homolog (DIABLO).</p> Conclusion <p>A causal relationship between mitochondrial biology and breast cancer was established in this study. ADPRase and COX8A were identified as protective factors, whereas PC, MRM3, COA3, and DIABLO were identified as risk factors.</p>

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Deciphering the causal nexus of mitochondrial biology with breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月26日

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  • Dongsong Liu,
  • Hongfang Xu,
  • Yan Yan,
  • Bingnan Wang,
  • Wangjun Yan

摘要

Background

The biological functions of mitochondria play a role in the occurrence and development of breast cancer, however, the causal relationship between them remains unclear.

Methods

Genetic instruments for mitochondrial biology and breast cancer were sourced from two genome-wide association studies (GWAS). Causal associations were assessed using Mendelian randomization analysis and validated through heterogeneity and sensitivity analyses. Additionally, the causal relationship between the identified mitochondrial proteins and the survival rate of breast cancer patients was further verified using the Kaplan-Meier Plotter.

Results

Analysis indicated causal associations between six mitochondrial proteins and breast cancer incidence. Inverse associations were found for ADP-ribose pyrophosphatase (ADPRase) and Cytochrome c oxidase subunit 8 A (COX8A), while positive correlations were observed for Pyruvate carboxylase (PC), rRNA methyltransferase 3 (MRM3), Cytochrome c oxidase assembly factor 3 homolog (COA3), and Diablo homolog (DIABLO).

Conclusion

A causal relationship between mitochondrial biology and breast cancer was established in this study. ADPRase and COX8A were identified as protective factors, whereas PC, MRM3, COA3, and DIABLO were identified as risk factors.