The Effect of Androgen Receptor Polymorphism on Endometrial Cancer (AREC)

December 12, 2021 updated by: Dionysis Vaidakis, University of Nicosia

The Effect of Androgen Receptor Polymorphism on Endometrial Cancer Development, Progression, and Outcome

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1
Patients with any type of endometrial cancer
Diagnostic test: Endometrial sampling and Peripheral blood collection
The endometrial biopsy will be performed with a pipette. The pipelle will be inserted gently through the cervix and into the uterus. The pipelle procedure takes approximately one minute and involves gently moving the pipelle back and forth to obtain a sample. Then 10cc of peripheral blood will be collected.
Behavioral: FSFI Scale

The participants will fill up the Female Sexual Function Index (FSFI) questionnaire.

The FSFI is a 19-item self-report questionnaire designed to measure sexual functioning in women. It assesses six domains of sexual function: sexual desire, sexual arousal, lubrication, orgasm, satisfaction, and pain (i.e., pain associated with vaginal penetration).
Group 2
Patients with hyperplastic endometrial lesion (all type of endometrial hyperplasia and endometrial polyps). In this group will be included the breast cancer survivors under tamoxifen.
Diagnostic test: Endometrial sampling and Peripheral blood collection
The endometrial biopsy will be performed with a pipette. The pipelle will be inserted gently through the cervix and into the uterus. The pipelle procedure takes approximately one minute and involves gently moving the pipelle back and forth to obtain a sample. Then 10cc of peripheral blood will be collected.
Behavioral: FSFI Scale

The participants will fill up the Female Sexual Function Index (FSFI) questionnaire.

The FSFI is a 19-item self-report questionnaire designed to measure sexual functioning in women. It assesses six domains of sexual function: sexual desire, sexual arousal, lubrication, orgasm, satisfaction, and pain (i.e., pain associated with vaginal penetration).
Control group
A random sample of women without any endometrial pathology.
Diagnostic test: Endometrial sampling and Peripheral blood collection
The endometrial biopsy will be performed with a pipette. The pipelle will be inserted gently through the cervix and into the uterus. The pipelle procedure takes approximately one minute and involves gently moving the pipelle back and forth to obtain a sample. Then 10cc of peripheral blood will be collected.
Behavioral: FSFI Scale

The participants will fill up the Female Sexual Function Index (FSFI) questionnaire.

The FSFI is a 19-item self-report questionnaire designed to measure sexual functioning in women. It assesses six domains of sexual function: sexual desire, sexual arousal, lubrication, orgasm, satisfaction, and pain (i.e., pain associated with vaginal penetration).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer vs control group
Time Frame: Day 1
DNA analysis is required for the CAG repeat testing procedure. The DNA will be isolated from venous white blood cells and from endometrial cells. The high-molecular-weight DNA will then be analysed by polymerase chain reaction (PCR) amplification protocols, the exon 1 of the androgen receptor gene will be located and the number of CAG repeats will be recorded. If PCR is not sufficient to determine the exact number of replicates per case, the nucleotide sequence of the PCR products will be determined.
Day 1
The length of CAG repeats on exon 1 of AR gene and the relation to benign lesions of the endometrium vs control group
Time Frame: Day 1
DNA analysis is required for the CAG repeat testing procedure. The DNA will be isolated from venous white blood cells and from endometrial cells. The high-molecular-weight DNA will then be analyzed by PCR amplification protocols, the exon 1 of the androgen receptor gene will be located and the number of CAG repeats will be recorded. If PCR is not sufficient to determine the exact number of replicates per case, the nucleotide sequence of the PCR products will be determined.
Day 1
The length of CAG repeats on exon 1 of AR gene as a predictive factor for endometrial lesions
Time Frame: Day 1
DNA analysis is required for the CAG repeat testing procedure. The DNA will be isolated from venous white blood cells and from endometrial cells. The high-molecular-weight DNA will then be analyzed by PCR amplification protocols, the exon 1 of the androgen receptor gene will be located and the number of CAG repeats will be recorded. If PCR is not sufficient to determine the exact number of replicates per case, the nucleotide sequence of the PCR products will be determined.
Day 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer stage at diagnosis among group 1 patients
Time Frame: Day 1
DNA analysis is required for the CAG repeat testing procedure. The DNA will be isolated from venous white blood cells and from endometrial cells. The high-molecular-weight DNA will then be analyzed by PCR amplification protocols, the exon 1 of the androgen receptor gene will be located and the number of CAG repeats will be recorded. If PCR is not sufficient to determine the exact number of replicates per case, the nucleotide sequence of the PCR products will be determined.
Day 1
The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer type among group 1 patients
Time Frame: Day 1
DNA analysis is required for the CAG repeat testing procedure. The DNA will be isolated from venous white blood cells and from endometrial cells. The high-molecular-weight DNA will then be analyzed by PCR amplification protocols, the exon 1 of the androgen receptor gene will be located and the number of CAG repeats will be recorded. If PCR is not sufficient to determine the exact number of replicates per case, the nucleotide sequence of the PCR products will be determined.
Day 1
The length of CAG repeats on exon 1 of AR gene and the relation to sexual function of the participants.
Time Frame: Day 1

DNA analysis is required for the CAG repeat testing procedure. The DNA will be isolated from venous white blood cells and from endometrial cells. The high-molecular-weight DNA will then be analyzed by PCR amplification protocols, the exon 1 of the androgen receptor gene will be located and the number of CAG repeats will be recorded. If PCR is not sufficient to determine the exact number of replicates per case, the nucleotide sequence of the PCR products will be determined.

The finding will be correlated with the answers of the participants in FSFI scale (Female Sexual Functioning Index )
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nicosia

Investigators

  • Principal Investigator: Maria Chryssi, MSh, Anticancer oncological hospital of Athens "St Savvas'
  • Study Director: Dionysios Vaidakis, MD,PhD., Department of Life & Health Sciences, University of Nicosia
  • Study Chair: Adonis Ioannides, MD,PhD., Department of Life & Health Sciences, University of Nicosia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

April 1, 2022

Primary Completion (ANTICIPATED)

April 1, 2023

Study Completion (ANTICIPATED)

April 1, 2024

Study Registration Dates

First Submitted

May 8, 2021

First Submitted That Met QC Criteria

December 12, 2021

First Posted (ACTUAL)

December 15, 2021

Study Record Updates

Last Update Posted (ACTUAL)

December 15, 2021

Last Update Submitted That Met QC Criteria

December 12, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DV001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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