Maternal Metabolic State and Cancer Risk: An Evolving Manifestation of Generational Impact

Abstract

Metabolic stress in the early-life environment as a consequence of maternal overnutrition and obesity leads to an increased risk of adult metabolic syndrome in offspring. Given the greater risk for cancer development at a number of tissue sites for obese individuals, exposure of the highly developmentally ``plastic{''} fetus and neonate to a dysregulated maternal endocrine milieu may similarly result in increased cancer susceptibility as adults. In rodent models, from which this concept has gained the most direct experimental support, the feedforward circuitry for cancer propensity appears to be generationally transmitted, in part, via epigenetic biochemical marks. Here, we review the current state of this nascent field with attention given to tissues that are likely impacted by the recent epidemic of maternal obesity. We highlight current thinking on underlying molecular mechanisms and discuss how such knowledge may be used to design interventional strategies for obese pregnant women to counter increased risk for malignancy in their offspring.