Epigenetic Bridge Between Oxidative Balance of Koreans and TCGA Pan-Cancer Risk: Sex-Specific DNA Methylation...

Area of Science:

• Epigenetics
• Cancer Epidemiology
• Nutritional Science

Background:

• Oxidative stress is linked to cancer, but epigenetic mechanisms connecting lifestyle factors to cancer risk are unclear.
• The Oxidative Balance Score (OBS) quantifies lifestyle factors influencing oxidative stress.

Purpose of the Study:

• To investigate the epigenetic link between OBS and pan-cancer susceptibility.
• To identify sex-specific epigenetic markers associated with OBS and cancer risk.

Main Methods:

• Calculated OBS for 2749 participants from the Korean Genome and Epidemiology Study (KoGES).
• Conducted epigenome-wide association analysis to identify OBS-associated CpG sites.
• Validated findings using The Cancer Genome Atlas (TCGA) pan-cancer dataset with a novel Hybrid Pi-score (HyPi).

Main Results:

• Identified profound sex-specific epigenetic signatures with no overlap in top OBS-associated CpG sites between males and females.
• Top 20 OBS-associated CpGs showed strong directional consistency with multiple cancer types in TCGA, inversely correlating with tumorigenesis.
• Observed sex-specific epigenetic signatures, with zero overlap in the top 200 OBS-associated CpG sites between males and females.

Conclusions:

• Provides the first evidence of an epigenetic link between lifestyle oxidative balance and pan-cancer risk.
• Highlights the utility of the HyPi score for sex-specific predictive biomarkers in cancer prevention.
• Suggests precision nutrition targeting oxidative balance may epigenetically modulate cancer susceptibility for personalized prevention.