P-127: Gestational diabetes mellitus and pediatric cancer risk: converging epigenetic, metabolic, and inflammatory pathways
B Shateri AmiriAbstract
Introduction
Gestational diabetes mellitus (GDM) not only alters the intrauterine environment but has also been linked to a higher risk of childhood cancer. Understanding the biological mechanisms behind this association is essential for developing preventive strategies for at-risk children.
Objectives
We aimed to integrate current knowledge on the main molecular pathways connecting maternal GDM to pediatric malignancies, with a focus on epigenetic changes, hyperglycemia, and hyperinsulinemia.
Methods
A comprehensive narrative review of published studies was performed. We gathered and synthesized evidence from cell biology, epigenetics, and signaling pathway analyses to identify converging mechanisms that drive cancer susceptibility.
Results
GDM-driven epigenetic dysregulation silences critical tumor suppressors (TP53, BRCA1, CDKN2A) and activates oncogenes (MYC, IGF2) through PI3K/AKT/mTOR and Wnt pathways. At the same time, maternal hyperglycemia fuels NF-κB-mediated inflammation, TGF-β-dependent epithelial-mesenchymal transition, and oxidative stress. Concurrent hyperinsulinemia enhances insulin/IGF-1 signaling, IL-17-related inflammation, and GPER/HIF-1α crosstalk. Importantly, several of these pathways have a dual role, being capable of both stimulating and restraining tumor formation depending on the cellular context.
Conclusions
Intertwined epigenetic, metabolic, and inflammatory disturbances caused by maternal GDM create a pro-oncogenic fetal milieu. These findings offer a mechanistic basis for identifying risk biomarkers and designing early protective interventions, reinforcing the importance of optimal glucose control during pregnancy for the lifelong health of the child.