Abstract 4638: Associations of fecal microbial profiles with non-malignant breast disease and breast cancer in the Ghana Breast Health Study
Authors: Byrd Doratha , Vogtmann Emily , Wu Zeni , Hullings Autumn , Hua Xing , Ahearn Thomas , Goedert James J. , Shi Jianxin , Figueroa Jonine , Brinton Louise , Garcia-Closas Montserrat , Sinha Rashmi 
Published: September 2020

Abstract
Background and objective: Breast cancer burden is rising in Africa; however, breast cancer risk factors remain largely understudied in this population. The gut microbiome may play a role in the etiology of breast cancer through the regulation of estrogen homeostasis and other metabolic or immunologic pathways. We investigated the association of fecal bacteria with breast neoplasms in a case-control study conducted in Accra and Kumasi, Ghana, comprising 102 non-malignant breast disease cases, 379 invasive breast cancer cases, and 414 population-based controls nested within the Ghana Breast Health Study.
Methods: We used the MO-BIO PowerMag kit for DNA extraction and sequenced the V4 region of 16S rRNA gene to characterize bacteria in fecal samples. We used DADA2 to process sequencing data. We calculated estimates of alpha diversity (observed sequence variants, Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray Curtis and unweighted/weighted UniFrac), and presence/absence and relative abundance of select taxa. We then estimated the associations of the microbial metrics with non-malignant breast disease and malignant breast cancer using multivariable unconditional logistic regression.
Results: Odds of malignant breast cancer were statistically significantly lower with increasing alpha diversity (all Ptrends &lt;0.0001). For example, comparing those in the highest vs. lowest tertile of observed sequence variants, the odds ratio and 95% confidence interval was 0.22 (0.13-0.36). Alpha diversity estimates were also lower for non-malignant breast disease cases compared to controls but were similar to malignant cases. Likewise, based on the multivariable MiRKAT test, which compares kernel similarity matrices based on beta diversity metrics, overall microbiota composition was similar between non-malignant and malignant cases (all p's &gt; 0.1) but was statistically significantly different for both case groups compared controls (all p's &lt;0.001). After correction for multiple testing, 49 taxa were significantly differentially prevalent among non-malignant and malignant cases compared to controls. Cases tended to have a lower prevalence of the Families Lachnospiraceae, Ruminococcaceae, and Prevotellaceae, and the genera Bifidobacterium, Collinsella, Coprococcus, and Mitsuokella. Notably, previous evidence suggests that some of these differentially prevalent taxa encode the enzymes ß-glucuronidase and/or ß-galactosidase, which are involved in estrogen metabolism.
Conclusions: Our findings suggest lower fecal alpha diversity, differences in overall microbial composition, and prevalence of certain taxa involved in estrogen metabolism may be associated with both non-malignant breast disease and invasive breast cancer. Given that the gut bacteria are potentially modifiable and targetable, our findings warrant further investigation into the role of the gut microbiota in hormone regulation and etiology of breast cancer in integrative, prospective studies.
Citation Format: Doratha Byrd, Emily Vogtmann, Zeni Wu, Autumn Hullings, Xing Hua, Thomas Ahearn, James J. Goedert, Jianxin Shi, Jonine Figueroa, Louise Brinton, Montserrat Garcia-Closas, Rashmi Sinha. Associations of fecal microbial profiles with non-malignant breast disease and breast cancer in the Ghana Breast Health Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4638.