Clinical trial NCT05157373: The Effect of Androgen Receptor Polymorphism on Endometrial Cancer
Official title: The Effect of Androgen Receptor Polymorphism on Endometrial Cancer Development, Progression, and Outcome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Androgen Receptor Abnormal
Endometrial Disorder
Keywords: Androgen Receptor
CAG
Receptor polymorphism
Lead sponsor: University of Nicosia
Sponsor class: OTHER
First posted: 2021-12-15
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will be conducted at 2 investigative sites in Greece and Cyprus. Recruitment will stop when approximately 150 patients are enrolled.

The study will be conducted at UNIC and will include patients from Anticancer Oncological Hospital of Athens ''Saint Savvas Hospital'' and from the researchers' private practices (control group and patients with benign endometrial lesions). All patients meeting the inclusion criteria below will be identified.

Up to 150 selected cases from among eligible patients will be enrolled in the study protocol.

Brief summary: Endometrial tissue is a hormonal-dependent tissue in both pre- and postmenopausal period. The endometrial cells are expressing receptors for all sex hormones, mainly for estrogen, progesterone and androgens. The proper response of the endometrial cells on hormones is crucial for a well-balanced fluctuation of endometrial tissue. If, for any reason, these responses are altered, this may lead to benign or malignant lesions.

The androgens, through their receptors, decrease the proliferation of the endometrial cells. After menopause, the number of androgens receptors (ARs) increases in proportion to estrogen receptors and this may lead to endometrial atrophy. If the functionality of ARs is decreased, the effect of estrogen increases and this may possibly lead to endometrial hyperplasia or to endometrial cancer. The AR gene is located on the X chromosome and consists of 8 exons. Genetic research has shown that on exon 1, there is an area of trinucleotide Cytosine- Adenosine- Guanin (CAG) repeats which controls the functionality of the receptor. The more CAG repeats, the less responsive the receptor.

The goal of this research is to study the AR gene polymorphism and particularly the number of CAG repeats on exon 1, in patients with known endometrial pathology (benign and malignant). The results will be compared with a random sample of the general population without endometrial pathology.

Detailed description: The role of CAG repeats on the AR is well established in degenerative neurological diseases in prostate and breast cancer, but the corresponding role in endometrial benign or malignant lesions is not well studied. It seems that there is a gap in the international literature since the results of the published studies are conflicting. A meta-analysis of 51 studies published by Qin et al. in 2017, suggested that the carriers of short polymorphic CAG repeats might increase the risk of prostate cancer, and could be used as a potential detecting marker. Another meta-analysis of 17 studies concluded that the longest CAG repeats increase the risk of breast cancer. Both those cancers are testosterone dependent and the higher the testosterone serum levels, the greater the cancer risk. Among women, the highest testosterone serum levels are observed in polycystic ovarian syndrome (PCOS) patients. A study published in 2020 concluded that the risk of PCOS is associated with the inheritance of ARs with shorter CAG repeats.Even though a meta-analysis of 11 studies demonstrate no evident association between the CAG length in AR gene and PCOS risk, the CAG length appears to be positively associated with higher testosterone levels. However, larger scale case-control studies are needed to validate the results. The rationale of the present study is to contribute to the literature by correlating the number of CAG repeats on AR with specific endometrial benign or malignant lesions. This may result in a better understanding of the nature of endometrial lesions and the development of specific clinical interventions.

The goal of this research is to study the AR gene polymorphism and particularly the number of CAG repeats on exon 1, in patients with known endometrial pathology (benign and malignant). The results will be compared with a random sample of the general population without endometrial pathology.

Impact on science, economy and society Adrenal receptor gene polymorphism seems to be related to many clinical conditions. Studying the AR gene polymorphism in relation to endometrial functionality will provide better understanding of the physiology of endometrial tissue function, the natural progression of endometrial lesions, as well as the potential of recurrence of those lesions after treatment. This may lead to the modification of therapeutic interventions and to the development of screening tests in high-risk populations.

Compliance Statement This study will be conducted in full accordance with all applicable research policies and procedures and all applicable laws and regulations. All episodes of noncompliance will be documented. The investigators will perform the study in accordance with this protocol, will obtain consent and assent, and will report unanticipated problems involving risks to subjects. Collection, recording, and reporting of data will be accurate and will ensure the privacy, health, and welfare of research subjects during and after the study.

Eligibility criteria: Inclusion Criteria

1. Women with histologically diagnosed primary endometrial cancer. All stages of endometrial cancer patients can be included in this group.
2. Women with the following endometrial lesion:

   1. Endometrial polyps
   2. Endometrial hyperplasia with and without atypia
   3. Endometrial hyperplasia after tamoxifen
3. Women with histologically proven normal endometrium

Exclusion Criteria:

1. Women with metastatic cancer in endometrium
2. Women with triple negative breast cancer
3. Women unable to consent

Primary outcomes:
measure: The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer vs control group
timeFrame: Day 1
measure: The length of CAG repeats on exon 1 of AR gene and the relation to benign lesions of the endometrium vs control group
timeFrame: Day 1
measure: The length of CAG repeats on exon 1 of AR gene as a predictive factor for endometrial lesions
timeFrame: Day 1
Secondary outcomes:
measure: The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer stage at diagnosis among group 1 patients
timeFrame: Day 1
measure: The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer type among group 1 patients
timeFrame: Day 1
measure: The length of CAG repeats on exon 1 of AR gene and the relation to sexual function of the participants.
timeFrame: Day 1
Other outcomes:
Locations:
Study officials:
affiliation: Anticancer oncological hospital of Athens "St Savvas'
name: Maria Chryssi, MSh
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Life & Health Sciences, University of Nicosia
name: Dionysios Vaidakis, MD,PhD.
role: STUDY_DIRECTOR
affiliation: Department of Life & Health Sciences, University of Nicosia
name: Adonis Ioannides, MD,PhD.
role: STUDY_CHAIR
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