Role of Irisin/FNDC5 (rs3480) Single Nucleotide Polymorphism in Breast Cancer

Breast cancer is the most frequent cancer in women worldwide. Its incidence is increasing but mortality has decreased in a considerable way due to the combined effect of early detection and improvement in treatment .

Irisin is encoded by the FNDC5 gene, whose expression is controlled by the peroxi- some proliferator activated receptor gamma coactivator 1 alpha (PGC-1α). PGC-1α is a transcriptional co-activator which does not bind directly to DNA. Studies indicated that the estrogen-related receptor alpha (ERRα) could be a factor that plays a role in PGC-1α binding to DNA. ERRα is encoded by the ESRRA gene and is an orphan nuclear receptor, which has two domains. One of them allows the interaction with DNA, and the second one with a ligand. The ERRα structure is similar to that of the estrogen receptor alpha (ERα), but this receptor does not bind to natural estrogens. ERRα interacts with a canonical sequence of the estrogen response elements (ERRE). ERRα and ERα could compete with each other to bind to similar DNA elements. Together, ERRα binds to DNA, in complex with PGC-1α, to regulate the activity of genes such as FNDC5 .

CA15-3, a high molecular weight glycoprotein (300-450 kDa), is produced by the epithelial ducts and acinic breast cells and is then secreted in milk normally. It has been widely used for the prediction of bone metastases in patients with breast cancer .

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Genetic: Genotyping

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Shimaa B Hemdan, lecturer; Phone Number: 01115894759; Email: shimaabadwy@med.sohag.edu.eg

Study Locations

• Egypt
  • Sohag, Egypt, Sohag
    • Sohag University Hospital
    • Contact: Magdy M Amin, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

A Case control study will be conducted on 100 patients with histologically confirmed breast cancer, and a control group of 50 healthy volunteers with no clinical evidence of any neoplastic disorder.

Description

Inclusion Criteria:

• histologically confirmed breast cancer

Exclusion Criteria:

• • History of other tumors.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
cases group; 50 patient of histologically confirmed breast cancer	Genetic: Genotyping; Genotyping of rs 3480 of irisin gene using the Taqman Allelic Discrimination assay technique.
control group; 50 healthy volunteers with no clinical evidence of any neoplastic disorder	Genetic: Genotyping; Genotyping of rs 3480 of irisin gene using the Taqman Allelic Discrimination assay technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
find a possible association between irisin gene single nucleotide polymorphism with breast cancer	- find a possible association between irisin gene single nucleotide polymorphism with breast cancer risk and the distribution of its alleles, in relation to many clinical parameters of the cancer group.	12 months

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• Peto R, Boreham J, Clarke M, Davies C, Beral V. UK and USA breast cancer deaths down 25% in year 2000 at ages 20-69 years. Lancet. 2000 May 20;355(9217):1822. doi: 10.1016/S0140-6736(00)02277-7. No abstract available.
• Balmain A, Gray J, Ponder B. The genetics and genomics of cancer. Nat Genet. 2003 Mar;33 Suppl:238-44. doi: 10.1038/ng1107.
• Nowinska K, Jablonska K, Ciesielska U, Piotrowska A, Haczkiewicz-Lesniak K, Pawelczyk K, Podhorska-Okolow M, Dziegiel P. Association of Irisin/FNDC5 with ERRalpha and PGC-1alpha Expression in NSCLC. Int J Mol Sci. 2022 Nov 17;23(22):14204. doi: 10.3390/ijms232214204.
• Fakhari A, Gharepapagh E, Dabiri S, Gilani N. Correlation of cancer antigen 15-3 (CA15-3) serum level and bony metastases in breast cancer patients. Med J Islam Repub Iran. 2019 Dec 19;33:142. doi: 10.34171/mjiri.33.142. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Soh-Med-23-04-10PD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No