Obesity and the breast cancer methylome

Breast cancer is associated with risk factors such as advancing age and obesity. However, the linkages between these risk factors for breast cancer development and initiation of the disease are not yet clear. Obesity may drive breast cancer development through increases in circulating estrogens in postmenopausal women. Mammary cell susceptibility to neoplastic transformation requires both genetic and epigenetic alterations, including changes in DNA methylation. Obesity is also subject to epigenetic regulation. In this review, the nature of epigenetic changes, specifically changes to the methylome, are discussed in the context of obesity and breast cancer, and a potential mechanism for the interaction of obesity and breast cancer is proposed. This proposed mechanism identifies opportunities for intervention (using drugs or biologic therapies) to prevent breast cancer development in the obese patient.