Abstract
BackgroundBreast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota.MethodsWe describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered.Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed.DiscussionThis is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.Trial registrationClinicalTrials.gov NCT03885648, 03/25/2019. Retrospectively registered.
Highlights
Breast cancer ranks first in women, and is the second cause of death in this gender
Plaza-Díaz et al BMC Cancer (2019) 19:495 (Continued from previous page). This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study
Evaluation of DNA damage by determination of phosphorylated histone 2AX (P-H2AX) Breast biopsies will be homogenized and seeded onto specific culture media to isolate bacterial colonies which later on will be evaluated based on their ability to generate nicks in the DNA of HeLa cells using the P-H2AX marker [27]
Summary
The environment contributes to the development of the disease, the factors involved are not well known Among the latter is the influence of microorganisms and, attention is recently being paid to the mammary microbiota. The function of the GI microbiota is to keep a dynamic equilibrium with the host, playing both local and remote roles [4] in important physiological processes, inflammation and the immune response [2]. This interspecies balance is named eubiosis [5]. A “disequilibrium” in the microbiota (referred to as dysbiosis) may lead to several human diseases [4]
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