2015
DOI: 10.1159/000441030
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Abstract: Age is the greatest risk factor for breast cancer, but the reasons underlying this association are unclear. While there is undeniably a genetic component to all cancers, the accumulation of mutations with age is insufficient to explain the age-dependent increase in breast cancer incidence. In this viewpoint, we propose a multilevel framework to better understand the respective roles played by somatic mutation, microenvironment, and epigenetics making women more susceptible to breast cancer with age. The proces… Show more

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Cited by 44 publications
(45 citation statements)
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“…Metastability is a physical concept, whereby an equilibrium state is stable for all intents and purposes, until acted upon by an external force. Aging may cause cells to transit across a continuum of metastable states, and these states may be maintained via epigenetic regulation[23]. In humans, aging is associated with changing DNA methylation states[2426], and an ‘epigenetic clock’ requiring only 353 CpG sites has been shown to provide a robust estimate of age across many tissue types[27].…”
Section: Variability In Agingmentioning
confidence: 99%
“…Metastability is a physical concept, whereby an equilibrium state is stable for all intents and purposes, until acted upon by an external force. Aging may cause cells to transit across a continuum of metastable states, and these states may be maintained via epigenetic regulation[23]. In humans, aging is associated with changing DNA methylation states[2426], and an ‘epigenetic clock’ requiring only 353 CpG sites has been shown to provide a robust estimate of age across many tissue types[27].…”
Section: Variability In Agingmentioning
confidence: 99%
“…Given that the aged mammary gland is associated with increased risk of diseases such as cancer both in mice and in human 27,43 , our findings may also provide initial insights into the underlying mechanisms of how aging contributes tumor development. For instance, alveolar luminal progenitor cells have been hypothesized as the cells-of-origin for triple-negative breast cancer 44-46 .…”
Section: Discussionmentioning
confidence: 80%
“…Proliferative and migratory behaviours supported by fibronectin and collagen I (Carey et al 2017) are similarly downregulated in older HMEC. Notably, the breast basal membrane becomes discontinuous with age in part due to hormonal changes during menopause (LaBarge et al 2015;Sympson 1994). Concurrently, collagen I and fibronectin deposition increases with age (Schedin & Keely 2011).…”
Section: Contextual Response Of Cells In An Ageing Microenvironment Imentioning
confidence: 99%