APOE ε4 Allele and Methylation Patterns Linked to Cardiovascular Outcomes in Women With Breast Cancer.

This article investigates the association between DNA methylation of the Apolipoprotein E (APOE) gene and cardiovascular (CV) risk factors and fitness in postmenopausal women with breast cancer (BC). Using data from a 6-month randomized exercise trial, the study found that APOE ε4 allele carriers exhibit differential methylation at specific CpG sites within the APOE gene, notably increased methylation at cg06750524, which was associated with higher odds of hypertension and lower cardiovascular fitness measured by VO2max/kg/min and metabolic equivalents (METs). Conversely, increased methylation at cg05501958 was linked to lower hypertension odds and better CV fitness. Neither APOE ε4 carrier status nor baseline methylation moderated the effects of the exercise intervention on cardiovascular outcomes. These findings suggest that APOE methylation patterns, varying by ε4 carriage, may serve as biomarkers for cardiovascular risk in women with breast cancer, warranting further research in broader populations.