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.

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.

Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers. In recent years, an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms. Obesity-induced abnormalities in immunity and biochemical metabolism, including chronic inflammation, hormonal disorders, dysregulation of adipokines, and microbial dysbiosis, may be important contributors to cancer development and progression. These contributors play different roles in cancer development and progression at different sites. Lifestyle changes, weight loss medications, and bariatric surgery are key approaches for weight-centered, obesity-related cancer prevention. Treatment of obesity-related inflammation and hormonal or metabolic dysregulation with medications has also shown promise in preventing obesity-related cancers. In this review, we summarize the mechanisms through which obesity affects the risk of cancer at different sites and explore intervention strategies for the prevention of obesity-associated cancers, concluding with unresolved questions and future directions regarding the link between obesity and cancer. The aim is to provide valuable theoretical foundations and insights for the in-depth exploration of the complex relationship between obesity and cancer risk and its clinical applications.
Humans ; Adipokines/metabolism* ; Bariatric Surgery ; Inflammation/therapy* ; Neoplasms/prevention & control* ; Obesity/therapy* ; Risk Factors