Impact of Physical Activity on DNA Methylation Signatures in Breast Cancer Patients: A Systematic Review with Bioinformatic Analysis

Simple Summary Breast cancer significantly affects women globally, but physical activity (PA) has been shown to improve the quality of life, aid recovery, and enhance survival rates in patients. Studies reveal that PA influences DNA methylation, both globally and at gene-specific levels, potentially reversing abnormal methylation linked to cancer. This review compiles research on PA's impact on DNA methylation in breast cancer patients. The findings suggest that PA increases global DNA methylation in tumour tissues and alters gene-specific promoter methylation across various genes. Bioinformatic analysis indicates that these genes are primarily involved in metabolic pathways, cell cycle regulation, mitosis, cellular stress responses, and diverse binding processes. The Human Protein Atlas supports these findings, showing gene functionality in 266 tissues, including various breast tissues. Overall, PA's ability to modify DNA methylation patterns in breast cancer patients may aid in the restoration of normal cellular functions and enhance recovery and survival outcomes.Abstract Breast cancer (BC) continues to significantly impact women worldwide. Numerous studies show that physical activity (PA) significantly enhances the quality of life, aids recovery, and improves survival rates in BC patients. PA's influence extends to altering DNA methylation patterns on both a global and gene-specific scale, potentially reverting abnormal DNA methylation, associated with carcinogenesis and various pathologies. This review consolidates the findings of the current literature, highlighting PA's impact on DNA methylation in BC patients. Our systematic analysis indicates that PA may elevate global DNA methylation within tumour tissues. Furthermore, it appears to modify gene-specific promoter methylation across a wide spectrum of genes in various tissues. Through bioinformatic analysis, to investigate the functional enrichment of these affected genes, we identified a predominant enrichment in metabolic pathways, cell cycle regulation, cell cycle checkpoints, mitosis, cellular stress responses, and molecular functions governing diverse binding processes. The Human Protein Atlas corroborates this enrichment, indicating gene functionality across 266 tissues, notably within various breast tissues. This systematic review unveils PA's capacity to systematically alter DNA methylation patterns across multiple tissues, particularly in BC patients. Emphasising its influence on crucial biological processes and functions, this alteration holds potential for restoring normal cellular functionality and the cell cycle. This reversal of cancer-associated patterns could potentially enhance recovery and improve survival outcomes.