PTGS2 and cancer: The lower incidence of cancers in the distal parts of the colorectum in women had been linked to direct and indirect anti-proliferative effects of estrogens, which are known to modulate COX-2 and CYP27B1/VDR expression: Thus, 17β-estradiol inhibits prostaglandin E2-induced COX-2 expression [26] and increases VDR and CYP27B1 expression and activity in cultured human colonocytes [27,28,29] as well as in human rectal epithelium in vivo [30].