BC is the most prevalent and leading fatal cancer type in women, yet the causes of most cases are unknown, indicating the necessity of deciphering contributing factors to quicken detection and inform therapeutic options. This research explores the relationship between the breast cancer (BC) genome and breast tissue bacteriome. BC forms in microenvironments in which genes and bacteria are in close proximity and research evidences gene-bacteria communication, but the relationship between the BC genome and the changing breast tissue bacteriome is not well understood. We hypothesized that genetic variation in the top ten genes commonly linked to BC: BRCA1, BRCA2, PTEN, TP53, PALB2, CHEK2, ATM, BRIP1, BARD1, and STK11would be associated with variations in the breast tissue bacteriome. We conducted 30X whole genome sequencing on 60 breast tissue samples (healthy, H (n=15), pre-diagnostic, PD (n=15), tumor, T (n=15), and adjacent normal, AN (n=15)) donated to the Susan G. Komen and Indiana University Simon Cancer Center Tissue Banks. These same samples were previously analyzed for microbiome composition and function using 16S rRNA sequencing (published in mSystems, 2022). Following sequence pre-processing, variant calling, and alternate allele frequency calculation by the UC Davis Bioinformatics Core, we selected only high and moderate variants for these genes with a quality score ≥ 55 for further analysis. Of the ten we intended to analyze, only 8 met these criteria within our data set: BRCA1, BRCA2, PTEN, TP53, PALB2, CHEK2, ATM, and BRIP1. We ran generalized linear models to select variants with differences in alternate allele frequency among the tissue types (H, PD, AN, T, p ≤ 0.2). Alternate allele frequencies and genotypes of these variants that passed this filter were then associated with bacterial ASVs deemed differentially abundant relative to the H tissue type (mSystems, 2022) using MaAsLin2. Three BC-linked genes BRCA1, TP53, and ATM show significant associations with the taxa, Muribaculaceae, Alcaligenes faecalis, Oceanobacillus, Romboutsia, Pseudomonas, and Pseudomonas fragi, at a p-value ≤ 0.01 and q-value ≤ 0.25. These genera belong to phyla (Bacteroides, Firmicutes, and Actinobacteria) which have been shown to either interact directly with the genome to produce cancer-causing DNA damage, or to be associated with other types of cancer, suggesting their likely role in tumorigenesis. The discovered associations further our understanding of the genetic and microbial determinants of breast cancer and may highlight the breast tissue bacteriome as a biomarker of BC.

Citation Format: Ariana McCaw, Rachel Jiang, Lindsey Marian, Leah Stiemsma. The breast cancer genome and its association with the breast tissue bacteriome [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A016.