Gut microbiota and risk of breast cancer: a bidirectional two-sample Mendelian randomization study
10.3760/cma.j.cn112309-20240409-00122
- VernacularTitle:肠道菌群与乳腺癌风险：双向两样本孟德尔随机化研究
- Author:
Hongxuan MA
1
;
Yuyuan ZHANG
;
Siyuan WENG
;
Hui XU
;
Yuhao BA
;
Shutong LIU
;
Zaoqu LIU
;
Xinwei HAN
Author Information
1. 郑州大学第一附属医院肾移植科，郑州 450052
- Publication Type:Journal Article
- Keywords:
Gut microbiota;
Breast cancer;
Causal relationships;
Mendelian randomization;
Single nucleotide polymorphism
- From:
Chinese Journal of Microbiology and Immunology
2025;45(2):125-134
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the potential causal relationships between gut microbiota composition and the risk of developing various subtypes of breast cancer by using bidirectional two-sample Mendelian randomization(MR).Methods:The research utilized genome-wide association studies(GWAS) data on gut microbiota from the MiBioGen database and GWAS data on breast cancer from the Breast Cancer Association Consortium (BCAC). In this MR study, inverse variance weighted (IVW), weighted median, MR Egger, and MR-PRESSO methods were used. Additionally, reverse MR and stratified analyses were conducted to assess reverse causality and the impact on different subtypes of breast cancer.Results:Adlercreutzia (IVW OR=0.92, 95% CI: 0.87-0.98, P=0.01) and Parabacteroides (IVW OR=0.87, 95% CI: 0.79-0.96, P=0.007) exhibited a statistically significant protective effect on breast cancer. Conversely, Sellimonas (IVW OR=1.05, 95% CI: 1.01-1.09, P=0.01) was significantly associated with an increased risk of breast cancer. Desulfovibrio (IVW OR=0.94, 95% CI: 0.88-1.00, P=0.04) and Ruminococcaceae (UCG013) (IVW OR=0.92, 95% CI: 0.86-0.99, P=0.03) presented suggestive protective effects against breast cancer. Furthermore, stratified analysis revealed that the protective effect of Adlercreutzia against breast cancer persisted in the estrogen receptor(ER)-positive subtypes, while Desulfovibrio persisted in the ER-negative subtypes. Sellimonas was causally associated with the risk of ER-positive subtypes. CACNA1S was identified as the functional gene of Adlercreutzia, and associated with favorable prognosis in breast cancer, while ERBB4 was identified as the functional gene of Sellimonas and associated with poor prognosis in breast cancer. Conclusions:This study identifies the causal relationships between gut microbiota and breast cancer, suggesting a novel target for early clinical intervention and treatment, with potential implications for future functional analysis.
