Abstract
The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.
Highlights
Breast cancer incidence and mortality are rising in sub-Saharan Africa [1]
Antibiotic use in the previous 30 days was more common among breast cancer cases than in non-malignant breast disease cases and controls
When excluding control stool samples collected at home or excluding those who used antibiotics within the previous 30 days, alpha diversity (Supplemental Table 7), beta diversity, relative abundance, and presence/absence associations were minimally affected. In this population-based case control study of breast cancer and non-malignant breast disease in Ghana, we found that 1) breast cancer and non-malignant breast disease cases had similar fecal microbial profiles, but different profiles from controls; 2) alpha diversity was strongly, inversely associated with breast cancer and non-malignant breast disease; 3) multiple taxa with multifunctional roles in estrogen metabolism and immune homeostasis, as described below, were associated with breast cancer and non-malignant breast disease; and, 4) alpha diversity was and strongly inversely associated with breast cancer by stage and molecular subtype, including estrogen receptor (ER) –/+ and triple-negative breast cancers
Summary
Breast cancer incidence and mortality are rising in sub-Saharan Africa [1]. Increasing breast cancer incidence in sub-Saharan Africa is likely due to the adoption of Westernized lifestyles, changes in reproductive factors, and population aging (due to increased life expectancy) [2,3,4]. Breast cancer risk factors remain understudied among African populations. It is likely that some established breast cancer risk factors (e.g., obesity) [5,6], in addition to other unknown risk factors, may influence the composition and function of the gut microbiota, including trillions of bacteria. The gut microbiota influences multiple pathways that are mechanistically linked to the initiation and growth of breast neoplasms [7,8,9,10]. Accumulating evidence supports the role of the gut microbiota in regulating endogenous estrogens [7,11] and systemic inflammation [12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
