Cancer and developmental origins of health and disease-epigenetic reprogramming as a mediator

Cancer cells are notorious for their ability to grow uncontrollably, evade apoptosis, accelerate metabolism, evade immunosurveillance, and invade distant organs before killing patients. Cancer cell phenotypes are driven by aberrant patterns of gene expression associated with massive chromosomal reshuffling and accumulation of mutations and epimutations. The “developmental origins of health and disease” (DOHaD) hypothesis posits that some cancers may have early life origins, namely, that suboptimal signaling or exposure to disruptive agents during critical periods of development reprograms the epigenome(s) of normal cells, predisposing them to higher risk of carcinogenesis later. Although much knowledge has emerged from studies of in utero reprogramming, we advocate the need to investigate other windows such as preconception; perinatal, peripubertal, and pubertal periods; pregnancy; and aging. We also discuss the merits of longitudinal human studies, disease-relevant animal models, and new technologies in helping identify “repressed memories” governing the complex, multistaged process of cancer etiology.