Impact of environmental and lifestyle changes on genetic alterations in breast cancer

Abstract

Breast cancer (BC) is the leading cause of death in women worldwide. It is one of the multifactorial and prevalent malignancies influenced by genetic, hormonal, environmental, and lifestyle-related risk factors. Increase in BC cases among women actively associated with social and professional life indicates the need for polydirectional research. This study presents a broad spectrum of established and emerging risk factors that contribute to the development of BC. Environmental agents and lifestyle habits potentially lead to microtubule degradation and hormonal imbalances in the body, exhibiting tumorigenesis in the mammary gland. The activation of these hormones poses negative impacts on the molecular pathway and a series of upregulated activities, leading to angiogenesis, cellular proliferation, and BC development. Ras/Raf/MEK, PI3K/AKT/mTOR, JAK/STAT, and C-Jun N-terminal kinase pathways get activated in this process, causing alterations in the transcriptional and translational factors. Mutations in the BRCA gene ultimately lead to failure of DNA repair and extracellular matrix remodeling through activation of the tumor microenvironment. This review presents an in-depth understanding of the risk factors and their role in genetic alteration in the induction of BC. Environmental and lifestyle changes, such as pesticides, heavy metals, and preservative exposures, act as endocrine disruptors for different steroidal hormones and melatonin. This association activates the PI3K and Ras/Raf/MEK pathway, leading to activation of CREB, c-Myc, and BRCA genes, causing breast cancer.