Deregulation of serum concentrations of E1 and E2, mainly through the higher activity of aromatase enzyme in the visceral adipose tissue combined with decreased liver production of SHBG, has been suggested as a mechanism leading to increased risk of breast cancer in postmenopausal women with obesity and T2D75,76. The gene discussed is SHBG; the disease is obesity due to melanocortin 4 receptor deficiency.