Abstract 3730: Oral microbiome and breast cancer risk in the NIH-AARP Diet and Health Study

Abstract Introduction: Breast cancer is the most commonly diagnosed cancer and leading cause of cancer death among women worldwide, with approximately 310, 720 new cases and 42, 250 deaths in 2024 in the US. The oral microbiome has been observed to be associated with breast cancer in case-control studies, but few studies have evaluated whether the oral microbiome may influence the risk of breast cancer. It has been hypothesized that the oral microbiome may be related to breast cancer risk through multiple mechanisms, including periodontal disease-related systemic inflammation or bacterial translocation. We evaluated the prospective association between the oral microbiome and breast cancer risk in the NIH-AARP Diet and Health Study cohort. Methods: The NIH-AARP cohort recruited 566, 398 participants aged 50 to 71 from 1995 to 1996. In 2005, 34, 262 oral wash specimens were collected by mail from a subset of living participants who had never been diagnosed with cancer and participants who had previously developed colorectal, breast, or prostate cancer. Within the women with an oral wash specimen without a prior cancer diagnosis, 348 women who later developed breast cancer were matched to a control using incidence density sampling by age at sample collection, race, and smoking history. DNA was extracted from the oral wash using the PowerSoil Pro, and shotgun metagenomic sequencing was conducted on the Illumina NovaSeq. After host filtering, the taxonomy of the unmapped reads was assigned using MetaPhlAn3, and functional profiling was performed using HUMAnN3. Relative abundances of the taxa from phylum to species level and the functional data of genes and pathways were calculated. Conditional logistic regression was conducted for alpha diversity, beta diversity, species-, and genes-level metrics to calculate odds ratios (OR) and 95% confidence intervals (CI) with adjustment for potential confounders including demographic and lifestyle characteristics, and reproductive factors. Results: The average age of participants was 61.5 (SD 5.2). The cases developed breast cancer an average of 3.4 years after the oral wash sample collection. There were no significant differences between cases and controls by education level, age at menarche, or menopausal status. Results from the first two batches of samples (44 cases and 44 controls) suggested that alpha diversity was inversely, but not statistically significantly, associated with breast cancer risk (e.g., OR observed species =0.79; 95% CI =0.45-1.40). Similarly, the presence of some periodontal pathogens was inversely, but not significantly, associated with breast cancer risk (e.g., OR Porphyromonas gingivalis =0.62; 95% CI =0.21-1.80). Conclusions: There are some indications that the oral microbiome may be prospectively associated with breast cancer risk. However, results from the complete dataset will provide better statistical power to adequately investigate potential associations. Citation Format: Giovanny A. Herrera Ossa, Xing Hua, Linda M. Liao, Yunhu Wan, Casey L. Dagnall, Kristine Jones, Belynda D. Hicks, Amy Hutchinson, Mitchell H. Gail, Jianxin Shi, Gretchen Gierach, Rashmi Sinha, Emily Vogtmann. Oral microbiome and breast cancer risk in the NIH-AARP Diet and Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3730.