Abstract
The androgen receptor (AR) poly‐glutamine polymorphism (AR‐Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR‐Qs and BaP in EMCA. During analysing patient AR‐Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR‐Q lengths (5‐year OS of 61.3% in Q length <20 and 88% in Q length >23). And AhR is higher expressed in short AR‐Q tumour compared to that in long AR‐Q patient. In vitro study found androgen‐response element (ARE) activity descends with AR‐Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR‐Q13 (but not AR‐Q25, or ‐35) enhances BaP‐induced dioxin‐responsive element (DRE) activity. Lastly, AR‐Q13 exerts higher colony‐forming capacity than other AR‐Qs, and knock‐down AhR abolished AR‐Q13‐mediated colony numbers. This study demonstrated a possible interaction of gene (AR‐Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large‐scale epidemiology and public health survey on the interaction of environmental toxin and AR poly‐Q in EMCA is suggested.
Highlights
endometrial cancer (EMCA) is one of the most common gynaecologic cancers in the Western world [1]
androgen receptor (AR) poly-Q length is negatively associated with EMCA progression and Aryl hydrocarbon Receptor (AhR) immunostaining intensity
The AR poly-Q length presented a normal distribution in the study population (Fig. 1A)
Summary
EMCA is one of the most common gynaecologic cancers in the Western world [1]. According to the National Cancer Institute, there are approximately 55,000 new cases diagnosed and 10,000 EMCA patients died each year in the United States [2]. Most EMCA develops after menopause [3]—a physiological condition defined by the lack of oestradiol or lower oestrogen levels than present during the fertile period of a woman’s life [4]. Epidemiological studies have described women with high plasma androgen levels as having an increased risk of developing EMCA [5]. This effect is attributed to local aromatization of oestrogens into androgens, which increases the mitogenic activity of tumour cells. Androgens can act on target tissues by interacting with the AR
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