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

Overview

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 Type

• Study Type: Observational
• Study Design
  • Time Perspective: Prospective
• Study Primary Completion Date: June 1, 2024

Interventions

• Genetic: Genotyping
  • Genotyping of rs 3480 of irisin gene using the Taqman Allelic Discrimination assay technique.

Arms, Groups and Cohorts

• cases group
  • 50 patient of histologically confirmed breast cancer
• control group
  • 50 healthy volunteers with no clinical evidence of any neoplastic disorder

Clinical Trial Outcome Measures

Primary Measures

• find a possible association between irisin gene single nucleotide polymorphism with breast cancer
  • Time Frame: 12 months
  • – 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.

Participating in This Clinical Trial

Inclusion Criteria

• histologically confirmed breast cancer Exclusion Criteria:

• • History of other tumors.

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: 70 Years

Investigator Details

• Lead Sponsor
  • Sohag University
• Provider of Information About this Clinical Study
  • Principal Investigator: Shimaa Badway Hemdan, lecturer of medical biochemistry – Sohag University
• Overall Contact(s)
  • Shimaa B Hemdan, lecturer, 01115894759, shimaabadwy@med.sohag.edu.eg

References

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.