Physical Activity, Global DNA Methylation and Breast Cancer Risk: A Systematic Literature Review and Meta-Analysis
A partir d'une revue systématique de la littérature (24 études), cette méta-analyse évalue l'association entre une activité physique, la méthylation globale de l'ADN et le risque de développer un cancer du sein
Background: The extent to which physical activity reduces breast cancer risk through changes in global DNA methylation is unknown. Methods: We systematically identified studies that investigated the association between: 1) physical activity and global DNA methylation; or 2) global DNA methylation and breast cancer risk. Associations were quantified using random-effects models. Heterogeneity was investigated through subgroup analyses and the Q-test and I2 statistics. Results: Twenty-four studies were reviewed. We observed a trend between higher levels of physical activity and higher levels of global DNA methylation (pooled standardized mean difference=0.19; 95% CI:-0.03-0.40; p=0.09) which, in turn, had a suggestive association with a reduced breast cancer risk (pooled relative risk=0.70; 95% CI:0.49-1.02; p=0.06). In subgroup analyses, a positive association between physical activity and global DNA methylation was observed among studies assessing physical activity over long periods of time (p=0.02). Similarly, the association between global DNA methylation and breast cancer was statistically significant for prospective cohort studies (p=0.007). Conclusions: Despite the heterogeneous evidence base, the literature suggests that physical activity reduces the risk of breast cancer through increased global DNA methylation. Impact: This study is the first to systematically overview the complete biologic pathway between physical activity, global DNA methylation, and breast cancer.