Abstract
BACKGROUND: As a novel index designed to quantify the dietary impact on gut microbiota, the Dietary Index for Gut Microbiota (DI-GM) remains unexplored in relation to breast cancer risk. This study aimed to explore the association between DI-GM and breast cancer risk and evaluate its combined effect with genetic risk. METHODS: A total of 96,195 participants from UK Biobank cohort were included in the study. DI-GM was constructed from 14 dietary components known to influence gut microbial diversity and was divided into three groups. A polygenic risk score (PRS) for breast cancer was constructed using 168 single-nucleotide polymorphisms to assess genetic risk. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up period of 12.86 years, 3,128 individuals developed breast cancer. In the multivariable-adjusted model, each point increase in DI-GM score was associated with a 5% reduction in breast cancer risk (95% CI: 0.92-0.99). Compared with those in low DI-GM, participants with high DI-GM were associated with a decreased breast cancer risk (HR: 0.89; 95% CI: 0.81-0.97). Joint analysis revealed that participants with high DI-GM and low PRS had a 35% lower risk of breast cancer compared with those in low DI-GM and high PRS (95% CI: 0.29-0.42). Notably, additive interactions were observed between DI-GM and PRS. Compared with individuals with low DI-GM, high DI-GM was significantly associated with a reduced breast cancer risk in individuals with low PRS (HR: 0.79; 95% CI: 0.65-0.97). CONCLUSION: Higher DI-GM was associated with a decreased risk of breast cancer, highlighting the importance of considering a gut microbiota-friendly diet in breast cancer precision prevention.