DNA Methylation and Epigenetic Modifications Linking Obesity, Insulin Resistance, and Cancer Risk

Ramzi Mohamed Adam Alnour

Kampala International University Teaching Hospital Ishaka

ABSTRACT

Obesity and insulin resistance are closely interconnected metabolic disorders that significantly elevate the risk of various cancers. Emerging evidence implicates epigenetic modifications, particularly DNA methylation, as pivotal mediators linking these conditions. DNA methylation is a heritable yet reversible epigenetic mechanism that regulates gene expression without altering the underlying DNA sequence. In the context of obesity, aberrant DNA methylation patterns have been identified in genes involved in adipogenesis, inflammation, insulin signaling, and tumorigenesis. Insulin resistance, characterized by impaired glucose uptake and chronic hyperinsulinemia, further exacerbates these epigenetic disruptions, creating a permissive environment for cancer initiation and progression. Additionally, lifestyle and environmental exposures, such as diet, physical activity, and early-life nutritional status, influence DNA methylation signatures and may program long-term disease susceptibility. This review explores the mechanistic roles of DNA methylation in obesity-induced insulin resistance and its downstream impact on cancer development. We discuss key methylated genes and pathways implicated in adipose tissue dysfunction, chronic inflammation, metabolic reprogramming, and cellular proliferation. Furthermore, we highlight recent advances in epigenome-wide association studies (EWAS), emerging biomarkers for early detection, and the potential for epigenetic therapies targeting modifiable methylation patterns. Understanding the epigenetic links between obesity, insulin resistance, and cancer opens new avenues for precision prevention and personalized treatment strategies in at-risk populations.

Keywords: DNA methylation, epigenetics, obesity, insulin resistance, cancer risk, adipose tissue, chronic inflammation

CITE AS: Ramzi Mohamed Adam Alnour (2025). DNA Methylation and Epigenetic Modifications Linking Obesity, Insulin Resistance, and Cancer Risk. NEWPORT INTERNATIONAL   JOURNAL OF SCIENTIFIC AND   EXPERIMENTAL SCIENCES 6(3):21-27 https://doi.org/10.59298/NIJSES/2025/63.2127