Miao Shichen, Ni Qichao, Fang Jun
Department of Thyroid and Breast Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
Breast J. 2024 Nov 6;2024:4434466. doi: 10.1155/2024/4434466. eCollection 2024.
This study aims to investigate the potential causal link between mitochondrial function and breast cancer using the Mendelian randomization (MR) analysis. The data used for this study were obtained from genomewide association studies (GWAS) databases on mitochondrial biological function and breast cancer. Mitochondrial function was considered the exposure variable, breast cancer the outcome variable, and specific single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs). Two MR methods, inverse variance weighting (IVW) and MR-Egger regression, were used to assess the causal association between mitochondrial function and breast cancer. Data analysis and visualization were performed using R software. The results of the analysis revealed that several genes, including 39S ribosomal protein L34, pyruvate carboxylase, rRNA methyltransferase 3, and cytochrome c oxidase assembly factor 3 homolog, are causally linked to an increased risk of breast cancer in European populations. In addition, cytochrome c oxidase subunit 8A and ADP-ribose pyrophosphatase were found to be protective factors against breast cancer in European populations. In East Asian populations, 39S ribosomal protein L52, ATP synthase subunit beta, and pyruvate dehydrogenase (acetyl-transferring) were identified as causal risk factors for breast cancer. Conversely, 39S ribosomal protein L32, ADP-ribose pyrophosphatase, and cytochrome c oxidase subunit 8A were identified as protective factors against breast cancer in this population. In conclusion, this study provides evidence of a causal relationship between mitochondrial function and breast cancer in both European and East Asian populations. Additional research is warranted to further elucidate the mechanisms underlying this association.
本研究旨在利用孟德尔随机化（MR）分析，探讨线粒体功能与乳腺癌之间潜在的因果关系。本研究使用的数据来自关于线粒体生物学功能和乳腺癌的全基因组关联研究（GWAS）数据库。线粒体功能被视为暴露变量，乳腺癌为结局变量，并选择特定的单核苷酸多态性（SNP）作为工具变量（IV）。采用两种MR方法，即逆方差加权（IVW）和MR-Egger回归，来评估线粒体功能与乳腺癌之间的因果关联。使用R软件进行数据分析和可视化。分析结果显示，包括39S核糖体蛋白L34、丙酮酸羧化酶、rRNA甲基转移酶3和细胞色素c氧化酶组装因子3同源物在内的几个基因，与欧洲人群患乳腺癌风险增加存在因果联系。此外，发现细胞色素c氧化酶亚基8A和ADP-核糖焦磷酸酶是欧洲人群中预防乳腺癌的保护因素。在东亚人群中，39S核糖体蛋白L52、ATP合酶β亚基和丙酮酸脱氢酶（乙酰转移）被确定为乳腺癌的因果风险因素。相反，在该人群中，39S核糖体蛋白L32、ADP-核糖焦磷酸酶和细胞色素c氧化酶亚基8A被确定为预防乳腺癌的保护因素。总之，本研究为欧洲和东亚人群中线粒体功能与乳腺癌之间的因果关系提供了证据。有必要进行进一步研究以进一步阐明这种关联背后的机制。
