Breast Cancer Exposomics

Abstract

We are exposed to a mixture of environmental man-made and natural xenobiotics. We experience a wide spectrum of environmental exposure in our lifetime, including the effects of xenobiotics on gametogenesis and gametes that undergo fertilization as the starting point of individual development and, moreover, in utero exposure, which can itself cause the first somatic or germline mutation necessary for breast cancer (BC) initiation. Most xenobiotics are metabolized or/and bioaccumulate and biomagnify in our tissues and cells, including breast tissues, so the xenobiotic metabolism plays an important role in BC initiation and progression. Many considerations necessitate a more valuable explanation regarding the molecular mechanisms of action of xenobiotics which act as genotoxic and epigenetic carcinogens. Thus, exposomics and the exposome concept are based on the diversity and range of exposures to physical factors, synthetic chemicals, dietary components, and psychosocial stressors, as well as their associated biologic processes and molecular pathways. Existing evidence for BC risk (BCR) suggests that food-borne chemical carcinogens, air pollution, ionizing radiation, and socioeconomic status are closely related to breast carcinogenesis. The aim of this review was to depict the dynamics and kinetics of several xenobiotics involved in BC development, emphasizing the role of new omics fields related to BC exposomics, such as environmental toxicogenomics, epigenomics and interactomics, metagenomics, nutrigenomics, nutriproteomics, and nutrimiRomics. We are mainly focused on food and nutrition, as well as endocrine-disrupting chemicals (EDCs), involved in BC development. Overall, cell and tissue accumulation and xenobiotic metabolism or biotransformation can lead to modifications in breast tissue composition and breast cell morphology, DNA damage and genomic instability, epimutations, RNA-mediated and extracellular vesicle effects, aberrant blood methylation, stimulation of epithelial-mesenchymal transition (EMT), disruption of cell-cell junctions, reorganization of the actin cytoskeleton, metabolic reprogramming, and overexpression of mesenchymal genes. Moreover, the metabolism of xenobiotics into BC cells impacts almost all known carcinogenic pathways. Conversely, in our food, there are many bioactive compounds with anti-cancer potential, exerting pro-apoptotic roles, inhibiting cell cycle progression and proliferation, migration, invasion, DNA damage, and cell stress conditions. We can conclude that exposomics has a high potential to demonstrate how environmental exposure to xenobiotics acts as a double-edged sword, promoting or suppressing tumorigenesis in BC.

Keywords: biologic pathways; breast cancer (BC); breast cancer risk (BCR); exposomics; xenobiotics.