INTERNATIONAL CONGRESS OF
CancerGenetics
The microbiome and its role in the development of breast cancer
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Asma Mohammadizade,1,*
1. Department of Microbiology, Faculty of Sciences, Kerman Branch, Islamic Azad University, Kerman, Iran
- Introduction: Despite extensive strategies in the diagnosis and treatment of cancer, breast cancer remains the most common cause of cancer death among women, and it is estimated that about 2.3 million women around the world are affected by it each year. Various factors such as race, age, family history, BRCA1/2 mutations, diet, physical inactivity, alcohol consumption, and estrogen levels affect the likelihood of developing the disease, its progression, and mortality (Stanisławek, 2021; Keyvani-Ghamsari et al., 2017). Since the breast has fatty tissue and extensive blood vessels, It is a suitable place for the growth and activity of various types of bacteria. Theories about bacterial presence include migration from skin through nipple ducts, oral contact, or translocation from the gut (Hieken et al., 2016). Theories about bacterial presence include migration from skin through nipple ducts, oral contact, or translocation from the gut (Hieken et al., 2016).
- Methods: In this review article, after monitoring the studies searched in the PubMed, Scopus, Web of Science, Google Scholar, ScienceDirect and SID.IR databases, Relevant articles from 2005 to 2022 were selected, and the role of the microbiome in breast cancer was examined accordingly.
- Results: In breast cancer, Changes in the gut microbiota can affect the incidence of this disease by affecting metabolism and estrogen-related or estrogen-independent mechanisms, Such as the effect on the immune system and production of metabolites (Ruo et al., 2021). Estrogen levels are very important in breast cancer. One of the main regulators of estrogen is the gut microbiota. Gut bacterial genes called estrobolome encode the enzyme β-glucuronidase, which deconjugates estrogen and converts it into its active form, so that it can bind to its receptors and activate intracellular cascades. Bacteria that produce β-glucuronidase include Escherichia, Citrobacter, Bifidobacterium, Bacteroides, and Clostridium (Ruo et al., 2021). Some gut microbes can also convert inactive steroid hormones into active steroids by producing sulfatase. In addition, the gut microbiota can convert dietary polyphenols into estrogen (Parida & Sharma, 2020; Baker et al., 2017). Therefore, changes in the amount and type of gut microbiota cause changes in estrogen levels and, as a result, affect the growth of breast cancer. In other words, estrogen levels are significantly dependent on the gut microbiota (Boccellino & D’Angelo, 2020). Lithocholic acid is a secondary bile acid. It is produced only by the gut microbiota from primary bile acids. Lithocholic acid reduces breast cancer cell proliferation by 10–20%, inhibits angiogenesis, and inhibits epithelial-to-mesenchymal transition, while increasing p53 expression and enhancing the antitumor immune response. It has been found that its levels are reduced in the early stages of breast cancer compared to the control group, which indicates a decrease in its synthesis by gut bacteria (Boccellino & D’Angelo, 2020; Zhang et al., 2019; Mikó et al., 2019; Mikó et al., 2018). Xuan and colleagues found in 2014 that in cancer tissue samples there is a significant reduction in bacterial communities compared to healthy breast tissue. A decrease in the amount of bacteria in a healthy person can increase the risk of breast cancer. It is predicted that bacteria stimulating host immune responses help maintain the healthy condition of breast tissue. Thompson et al. in 2017 found that in breast tumor tissue Proteobacteria are abundant, while Actinobacteria are prominently seen in surrounding non-tumorous tissue. They also reported that the amount of Streptococcus pyogenes increases in tumor tissue, which is a bacterium associated with increased systemic estrogen via β-glucuronidase activity, and it increases the risk of breast cancer (Thompson et al., 2017).
- Conclusion: Studies and evidence show that the microbiota in the breast and intestines are important for the development or prevention of breast cancer. Changes in the composition and amount of bacteria in these areas can be caused by an impact on Estrogen metabolism, regulation of the immune system, production of protective or destructive metabolites, and inflammatory responses may affect the carcinogenesis process. Accurate identification of the bacterial species involved and understanding their mechanisms can provide new perspectives in prevention, early detection, and design of new treatments for breast cancer. Therefore, it seems essential to investigate microbiota as a complementary approach in breast cancer research.
- Keywords: Microbiota, dysbiosis, Carcinogenesis, Estrogen, Metabolites
