Association between Estrogen-Related Genetics and Microbial Factors in Breast Tissue
Presentation Type
Poster
Presentation Type
Submission
Keywords
breast cancer, estrogen pathway genetics, estrogen metabolism, estrobolome, mammary microbiome, breast tumor, breast microbiome, breast cancer genetics, breast tissue, breast cancer genomics
Department
Biology
Major
Biology
Abstract
Breast cancer (BC) is the most prevalent cancer globally for women. It is also a multifactorial disease with both genetic and environmental determinants. Estrogen is critically related to BC and heavily studied, but the association between the breast tissue microbiome and estrogen pathway genetics is currently unknown.
We hypothesized that the genetic variation (alternate allele frequency and genotype) in and the expression of estrogen pathway genes are associated with variations in local breast tissue microbes (top BC-associated and estrogen-metabolizing microbes). Using microbiome-GWAS analysis on 60 donated breast tissue samples (healthy, pre-diagnostic, tumor, and adjacent normal), we filtered out significant variants BCL2A1, BCL2L10, ESRRB, FOSL2-AS1, MAPK10, NOS3, RAF1, and RASGRP4 based on their association with breast cancer. These genes were then associated with differentially abundant bacterial ASVs and alpha diversity metrics using MaAsLin2. We also analyzed the expression of select variants, RAF1 and BCL2L10, via qPCR.
Our study found five significant associations between frequencies (FOSL2-AS1 and RASGRP4) with bacterial taxa (Lactobacillus, Bacteroides, and Streptococcus), 21 associations between genotypes (BCL2A1, BCL2L10, ESRRB, MAPK10, NOS3, RAF1, and RASGRP4) with bacterial taxa (Bacteroides, Bradyrhizobium, Carnobacteriu, Dermabacter, Fusobacterium, Lactobacillus, Proteus, Sphingomonas, Streptococcus, and Tissierella), genotype-tissue associations for the Mut/Mut genotype of ESRRB and MAPK10 with cancer tissue types (PD, AN, and T), and associations between estrobolome β-glucuronidase and/or β-glucosidase producers with estrogen pathway genes. We located no significant associations between alpha diversity with genetic variations and between gene expression of RAF1 and BCL2L10 with gene frequency, genotype, and microbial taxa.
Faculty Mentor
Leah Stiemsma
Funding Source or Research Program
Academic Year Undergraduate Research Initiative, Summer Undergraduate Research in Biology
Location
Waves Cafeteria
Start Date
22-3-2024 1:30 PM
End Date
22-3-2024 2:30 PM
Association between Estrogen-Related Genetics and Microbial Factors in Breast Tissue
Waves Cafeteria
Breast cancer (BC) is the most prevalent cancer globally for women. It is also a multifactorial disease with both genetic and environmental determinants. Estrogen is critically related to BC and heavily studied, but the association between the breast tissue microbiome and estrogen pathway genetics is currently unknown.
We hypothesized that the genetic variation (alternate allele frequency and genotype) in and the expression of estrogen pathway genes are associated with variations in local breast tissue microbes (top BC-associated and estrogen-metabolizing microbes). Using microbiome-GWAS analysis on 60 donated breast tissue samples (healthy, pre-diagnostic, tumor, and adjacent normal), we filtered out significant variants BCL2A1, BCL2L10, ESRRB, FOSL2-AS1, MAPK10, NOS3, RAF1, and RASGRP4 based on their association with breast cancer. These genes were then associated with differentially abundant bacterial ASVs and alpha diversity metrics using MaAsLin2. We also analyzed the expression of select variants, RAF1 and BCL2L10, via qPCR.
Our study found five significant associations between frequencies (FOSL2-AS1 and RASGRP4) with bacterial taxa (Lactobacillus, Bacteroides, and Streptococcus), 21 associations between genotypes (BCL2A1, BCL2L10, ESRRB, MAPK10, NOS3, RAF1, and RASGRP4) with bacterial taxa (Bacteroides, Bradyrhizobium, Carnobacteriu, Dermabacter, Fusobacterium, Lactobacillus, Proteus, Sphingomonas, Streptococcus, and Tissierella), genotype-tissue associations for the Mut/Mut genotype of ESRRB and MAPK10 with cancer tissue types (PD, AN, and T), and associations between estrobolome β-glucuronidase and/or β-glucosidase producers with estrogen pathway genes. We located no significant associations between alpha diversity with genetic variations and between gene expression of RAF1 and BCL2L10 with gene frequency, genotype, and microbial taxa.