Mechanistic considerations for reduced endometrial cancer risk by smoking

Abstract

This review provides mechanistic explanations on why smoking reduces endometrial cancer risk with the primary focus on polyaromatic hydrocarbons (PAHs). PAHs from cigarette smoke can activate aryl hydrocarbon receptor–mediated pathways. This leads to (i) increased levels of anticarcinogenic metabolites of estradiol, (ii) suppression of estrogen receptor (ER)–mediated actions, and (iii) induction of endometrial apoptosis. In addition, hydroxylated metabolites of PAHs may also evoke antitumor effects via the ER, specifically ERβ. The nuclear receptor expression profile in the human endometrium continuously changes throughout the menstrual cycle. In addition, endometrial apoptosis plays a fundamental role in the regulation of the menstrual cycle. The dynamic ER, progesterone receptor, and aryl hydrocarbon receptor expression together with the importance of apoptosis in the human endometrium likely explains the anticarcinogenic effect of PAHs from smoking on the endometrium as opposed to that on the mammary gland.