Mechanistic considerations for reduced endometrial cancer risk by smoking

Martin van den Berg, Majorie B.M. van Duursen

Research output: Contribution to JournalReview articleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalCurrent Opinion in Toxicology
Volume14
DOIs
Publication statusPublished - Apr 2019

Fingerprint

Endometrial Neoplasms
Hydrocarbons
Estrogen Receptors
Smoking
Endometrium
Apoptosis
Menstrual Cycle
Metabolites
Anticarcinogenic Agents
Aryl Hydrocarbon Receptors
Progesterone Receptors
Human Mammary Glands
Cytoplasmic and Nuclear Receptors
Smoke
Tobacco Products
Estradiol

Keywords

  • Apoptosis
  • Aryl hydrocarbon receptor
  • Endometrial cancer
  • Estrogen metabolism
  • PAHs
  • Smoking

Cite this

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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.",
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Mechanistic considerations for reduced endometrial cancer risk by smoking. / van den Berg, Martin; van Duursen, Majorie B.M.

In: Current Opinion in Toxicology, Vol. 14, 04.2019, p. 52-59.

Research output: Contribution to JournalReview articleAcademicpeer-review

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