Mendelian randomization analysis revealed a gut microbiota–mammary axis in breast cancer

Frontiers in Microbiology

Microbiology

Wenchuan Zhang¹  Haiyue Ren¹  Zitong Wang¹  Zhe Wang²  Qingjie Lv²  Shuwan Zhang²  Rui Xue³ 

[1] Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China;Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China;Key Laboratory of Intelligent and Precision Pathology Diagnosis in Oncology, China Medical University, Shenyang, Liaoning, China;School of Medicine, Chongqing University, Chongqing, China;

关键词: breast cancer;    gut microbiota;    genus;    mendelian randomization;    pathogenesis;   

DOI  :  10.3389/fmicb.2023.1193725

 received in 2023-04-04, accepted in 2023-08-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundObservational epidemiological studies suggested an association between the gut microbiota and breast cancer, but it remains unclear whether the gut microbiota causally influences the risk of breast cancer. We employed two-sample Mendelian randomization (MR) analysis to investigate this association.MethodsWe used summary statistics of the gut microbiome from a genome-wide association study (GWAS) of 18,340 individuals in the MiBioGen study. GWAS summary statistics for overall breast cancer risk and hormone receptor subtype-specific analyses were obtained from the UK Biobank and FinnGen databases, totaling 400,000 individuals. The inverse variance-weighted (IVW) MR method was used to examine the causal relationship between the gut microbiome and breast cancer and its subtypes. Sensitivity analyses were conducted using maximum likelihood, MR-Egger, and MR pleiotropic residual sums and outliers methods.ResultsThe IVW estimates indicated that an increased abundance of Genus_Sellimonas is causally associated with an increased risk of ER+ breast cancer [odds ratio (OR) = 1.09, p = 1.72E−04, false discovery rate (FDR) = 0.02], whereas an increased abundance of Genus_Adlercreutzia was protective against ER+ breast cancer (OR = 0.88, p = 6.62E−04, FDR = 0.04). For Her2+ breast cancer, an increased abundance of Genus_Ruminococcus2 was associated with a decreased risk (OR = 0.77, p = 4.91E−04, FDR = 0.04), whereas an increased abundance of Genus_Erysipelatoclostridium was associated with an increased risk (OR = 1.25, p = 6.58E−04, FDR = 0.04). No evidence of heterogeneity or horizontal pleiotropy was found.ConclusionOur study revealed a gut microbiota–mammary axis, providing important data supporting the potential use of the gut microbiome as a candidate target for breast cancer prevention, diagnosis, and treatment.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Zhang, Ren, Xue, Wang, Wang and Lv.