Oral microbiome and postmenopausal breast cancer risk: findings from the NIH-AARP diet and health study.

Introduction: Breast cancer is the most frequently diagnosed cancer among women worldwide. Some case-control studies have reported associations between the oral microbiome and breast cancer, but the temporality of the association remains unclear. Therefore, we examined this association prospectively in the NIH-AARP Diet and Health Study. Methods: In 2005, oral wash samples were collected from a subset of the NIH-AARP cohort. We identified 318 women who developed breast cancer after collection and 318 controls, incidence-density matched on age at collection, race/ethnicity and smoking. DNA was extracted using the DNeasy PowerSoil Pro Kit, followed by shotgun metagenomic sequencing. Conditional logistic regression was used to calculate the odds ratios (OR) for associations between alpha- and beta-diversity and species- and gene-level metrics with breast cancer risk, adjusting for potential confounders. Results: Cases developed breast cancer on average 3.4 years after sample collection. Overall, the majority of the microbial metrics, including species and genes, showed largely null associations with the exception of Pielou's evenness (OR = 0.82; 95% CI = 0.70-0.95). When stratified by time to diagnosis, the inverse association with Pielou's evenness was only detected among women diagnosed within 2 years (29% of cases). In this subgroup, some previously reported associations, like the inverse association with the presence of Conclusions: The oral microbiome was generally not prospectively associated with postmenopausal breast cancer in a US population and results suggested previous findings may reflect reverse causation.