Gut microbiota and breast cancer risk: a Mendelian randomization study stratified by ER status
Abstract Background The potential causal relationship between gut microbiota (GM) and breast cancer (BC), particularly its estrogen receptor (ER)-positive (ER+) and ER-negative (ER−) subtypes, remains insufficiently characterized. Method We conducted a two-sample Mendelian randomization (MR) analysi...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-08-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-03379-1 |
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| Summary: | Abstract Background The potential causal relationship between gut microbiota (GM) and breast cancer (BC), particularly its estrogen receptor (ER)-positive (ER+) and ER-negative (ER−) subtypes, remains insufficiently characterized. Method We conducted a two-sample Mendelian randomization (MR) analysis to examine genetically predicted causal associations between 473 GM features (abundance in stool) and BC, including overall BC (Ncase = 24,270, Ncontrol = 222,078), ER+ BC (Ncase = 14,540, Ncontrol = 221,705) and ER– BC (Ncase = 9,724, Ncontrol = 221,705). Result The MR results demonstrated differential causal associations between GM and BC subtypes: For overall BC risk, lower Barnesiella abundance (OR = 0.93; 95%CI 0.88–0.98; P = 0.006) was protective, whereas higher Providencia abundance (OR = 1.30; 95%CI 1.11–1.51; P = 0.0008) increased risk. Among ER+ BC cases, five GM showed significant associations: Dokdonella (OR = 1.38; 95%CI 1.12–1.70; P = 0.0024), Flavonifractor sp900199495 (OR = 0.81; 95%CI 0.69–0.94; P = 0.0054), Rhodanobacter (OR = 1.45; 95%CI 1.10–1.92; P = 0.0087), Ruminococcus (OR = 0.73; 95%CI 0.58–0.92; P = 0.0080), and UBA7177 sp002491225 (OR = 1.33; 95%CI 1.08–1.63; P = 0.0067). In ER− BC, seven GM factors exhibited causal relationships: Bacteroides A plebeius (OR = 0.90; 95%CI 0.84–0.97; P = 0.0077), CAG-273 sp003507395 (OR = 0.89; 95%CI 0.82–0.95; P = 0.0009), CAG-390 sp003523225 (OR = 0.82; 95%CI 0.71–0.95; P = 0.0064), CAG-433 (OR = 0.86; 95%CI 0.78–0.95; P = 0.0030), Chromobacteriaceae (OR = 0.57; 95%CI 0.39–0.83; P = 0.0034), Providencia (OR = 1.48; 95%CI 1.18–1.86; P = 0.0007), and Syntrophorhabdaceae (OR = 1.52; 95%CI 1.14–2.04; P = 0.0050). Conclusions Our genetically informed MR analysis provides suggestive evidence for the differential causal roles of specific GM in overall, ER + and ER− BC pathogenesis, offering potential biomarkers for therapeutic intervention strategies. |
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| ISSN: | 2730-6011 |