The impact of the fetal exposome as a predictor of cancer risk in childhood and adulthood. Aberrant epigenetic events occurring during gestation: May they trigger fetal programming of cancer risk later in life?

Abstract

The rising incidence of cancer, particularly among children and young adults, has led to renewed interest in the early-life origins of the disease. The fetal programming hypothesis, originally proposed by Barker, posits that environmental disruptions during intrauterine development can induce long-lasting molecular and structural changes that increase susceptibility to diseases, including cancer, later in life. This narrative review examines how prenatal exposures, such as maternal malnutrition, alcohol use, exposure to toxins, obesity, and hormonal imbalances, may epigenetically reprogram the developing fetus, influencing cancer risk throughout the lifespan. We summarize mechanistic evidence from both epidemiologic studies and preclinical models, highlighting the roles of altered DNA methylation, growth factor signaling, and inflammation. While we emphasize fetal life as a critical window for cancer prevention, we also acknowledge alternative explanations for the rising cancer rates among younger populations, including improved diagnostics and lifestyle factors. Gaining an understanding of these early-life determinants of cancer may lead to new opportunities for targeted prevention strategies that begin before birth.