The Effect of Androgen Receptor Polymorphism on Endometrial Cancer

NCT05157373 | Unknown

• 1 other identifier: DV001
• Study Type: observational
• Target: 150
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Androgen Receptor Abnormal; Endometrial Disorder

Keywords

Androgen Receptor; CAG; Receptor polymorphism

Outcome Measures

Primary Outcomes (3)

• The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer vs control group

  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

  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

  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 Outcomes (3)

• The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer stage at diagnosis among group 1 patients

  Day 1

• The length of CAG repeats on exon 1 of AR gene and the relation to endometrial cancer type among group 1 patients

  Day 1

• The length of CAG repeats on exon 1 of AR gene and the relation to sexual function of the participants.

  Day 1

Study Arms (3)

Group 1

Patients with any type of endometrial cancer

Diagnostic Test: Endometrial sampling and Peripheral blood collection; Behavioral: FSFI Scale

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; Behavioral: FSFI Scale

Control group

A random sample of women without any endometrial pathology.

Diagnostic Test: Endometrial sampling and Peripheral blood collection; Behavioral: FSFI Scale

Interventions

Endometrial sampling and Peripheral blood collection DIAGNOSTIC_TEST

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.

Control group; Group 1; Group 2

FSFI Scale BEHAVIORAL

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; Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 90 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Women with histologically diagnosed primary endometrial cancer. All stages of endometrial cancer patients can be included in this group.
• Women with the following endometrial lesion:
• Endometrial polyps
• Endometrial hyperplasia with and without atypia
• Endometrial hyperplasia after tamoxifen
• Women with histologically proven normal endometrium

You may not qualify if:

• Women with metastatic cancer in endometrium
• Women with triple negative breast cancer
• Women unable to consent

Sponsors & Collaborators

• University of Nicosia: lead

Related Publications (11)

• Chuffa LG, Lupi-Junior LA, Costa AB, Amorim JP, Seiva FR. The role of sex hormones and steroid receptors on female reproductive cancers. Steroids. 2017 Feb;118:93-108. doi: 10.1016/j.steroids.2016.12.011. Epub 2016 Dec 29.

  PMID: 28041951 RESULT

• Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update. 2017 Mar 1;23(2):232-254. doi: 10.1093/humupd/dmw042.

  PMID: 27920066 RESULT

• Maybin JA, Critchley HO. Menstrual physiology: implications for endometrial pathology and beyond. Hum Reprod Update. 2015 Nov-Dec;21(6):748-61. doi: 10.1093/humupd/dmv038. Epub 2015 Aug 7.

  PMID: 26253932 RESULT

• Zitzmann M, Nieschlag E. The CAG repeat polymorphism within the androgen receptor gene and maleness. Int J Androl. 2003 Apr;26(2):76-83. doi: 10.1046/j.1365-2605.2003.00393.x.

  PMID: 12641825 RESULT

• Qin Z, Li X, Han P, Zheng Y, Liu H, Tang J, Yang C, Zhang J, Wang K, Qi X, Tang M, Wang W, Zhang W. Association between polymorphic CAG repeat lengths in the androgen receptor gene and susceptibility to prostate cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2017 Jun;96(25):e7258. doi: 10.1097/MD.0000000000007258.

  PMID: 28640128 RESULT

• Mao Q, Qiu M, Dong G, Xia W, Zhang S, Xu Y, Wang J, Rong Y, Xu L, Jiang F. CAG repeat polymorphisms in the androgen receptor and breast cancer risk in women: a meta-analysis of 17 studies. Onco Targets Ther. 2015 Aug 13;8:2111-20. doi: 10.2147/OTT.S85130. eCollection 2015.

  PMID: 26316780 RESULT

• Student S, Hejmo T, Poterala-Hejmo A, Lesniak A, Buldak R. Anti-androgen hormonal therapy for cancer and other diseases. Eur J Pharmacol. 2020 Jan 5;866:172783. doi: 10.1016/j.ejphar.2019.172783. Epub 2019 Nov 8.

  PMID: 31712062 RESULT

• Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016 Oct;37(5):467-520. doi: 10.1210/er.2015-1104. Epub 2016 Jul 26.

  PMID: 27459230 RESULT

• Polat S, Karaburgu S, Unluhizarci K, Dundar M, Ozkul Y, Arslan YK, Karaca Z, Kelestimur F. The role of androgen receptor CAG repeat polymorphism in androgen excess disorder and idiopathic hirsutism. J Endocrinol Invest. 2020 Sep;43(9):1271-1281. doi: 10.1007/s40618-020-01215-7. Epub 2020 Mar 12.

  PMID: 32166698 RESULT

• Baculescu N. The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS. J Med Life. 2013 Mar 15;6(1):18-25. Epub 2013 Mar 25.

  PMID: 23599814 RESULT

• Zhang T, Liang W, Fang M, Yu J, Ni Y, Li Z. Association of the CAG repeat polymorphisms in androgen receptor gene with polycystic ovary syndrome: a systemic review and meta-analysis. Gene. 2013 Jul 25;524(2):161-7. doi: 10.1016/j.gene.2013.04.040. Epub 2013 Apr 26.

  PMID: 23628801 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

endometrial tissue and serum

MeSH Terms

Conditions

Bulbo-Spinal Atrophy, X-Linked

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Maria Chryssi, MSh

  Anticancer oncological hospital of Athens "St Savvas'

  PRINCIPAL INVESTIGATOR

• Dionysios Vaidakis, MD,PhD.

  Department of Life & Health Sciences, University of Nicosia

  STUDY DIRECTOR

• Adonis Ioannides, MD,PhD.

  Department of Life & Health Sciences, University of Nicosia

  STUDY CHAIR

Central Study Contacts

Dionysios Vaidakis, MD,PhD.

CONTACT

00306976355332; Vaidakis.d@unic.ac.cy

Maria Chryssi, MSh

CONTACT

00306936660243; m.chryssi@yahoo.gr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: May 8, 2021
• First Posted: December 15, 2021
• Study Start: April 1, 2022
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2024
• Last Updated: December 15, 2021

Record last verified: 2021-12