Obesity related Methylation markers for obesity-related cancers

Project Summary This research project proposes to utilize existing leukocyte DNA methylation data to better understand biological pathways responsible for positive associations between obesity and risk of 13 distinct cancers. Recent Epigenome-Wide Association Studies (EWAS) have identified consistent blood leukocyte DNA methylation markers of obesity. Intriguingly, several of these obesity-related methylated markers, discovered in EWAS, are closely tied to key carcinogenic mechanisms, such as insulin resistance and diabetes, underscoring their significance in cancer. By leveraging the extensive and diverse data from the Atherosclerosis Risk in Communities Study (ARIC), we aim to identify specific adiposity-related DNA methylation markers associated with obesity-related cancers. Central to our research is the hypothesis that a subset of adiposity-related DNA methylation markers can provide a comprehensive and nuanced understanding of the mechanisms driving obesity-related cancers. Our planned endeavors include the identification of adiposity-related methylation markers that have a strong and precise association with obesity-related cancers, and an exploration of their gene ontology to characterize the genes and regulatory components that influence obesity-related carcinogenesis, potentially unveiling novel underlying pathways. Furthermore, we are proposing to develop and validate a composite DNA methylation score that surpasses conventional metrics like BMI in predicting obesity-related cancer risks. Given the limitations of conventional measures in capturing the multifaceted biology of adiposity, our focus on DNA methylation, especially in light of its potential modifiability, will position it as an invaluable tool for risk assessment and monitoring the impact of weight fluctuations on cancer risk. This proposed project stands at the forefront of innovative data analysis, setting the stage for a transformative understanding of obesity-related carcinogenesis and paving the way for enhanced preventive strategies.