The oral microbiome and breast cancer and non-malignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and non-malignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 non-malignant cases, and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard, and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and non-malignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared with controls. Beta-diversity was also associated with breast cancer and non-malignant breast disease compared with controls (P≤0.001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared with controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r=-0.37, P≤0.001). Many oral microbial metrics were strongly associated with breast cancer and non-malignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.