A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism

Area of Science:

• Genetics
• Oncology
• Chronobiology

Background:

• The PERIOD 3 (PER-3) gene, located on chromosome 1p36.23, exhibits polymorphism with 4 or 5 tandem repeat copies.
• PER-3 gene polymorphisms are implicated in immune system dysregulation.
• Understanding the role of circadian gene PER-3 in multiple myeloma (MM) is crucial for treatment strategies.

Purpose of the Study:

• To investigate the distribution and clinical impact of PER-3 gene polymorphism in multiple myeloma patients.
• To evaluate the association between PER-3 genotypes and patient survival outcomes, including overall survival (OS) and progression-free survival (PFS).

Main Methods:

• A case-control study involving 150 MM patients and 100 healthy controls.
• Genotyping of the PER-3 gene was performed before treatment initiation.
• Statistical comparison of genotype distributions and analysis of PER-3's effect on OS and PFS post-treatment, including autologous stem cell transplantation (ASCT) and maintenance therapy (LD).

Main Results:

• The 5R/5R genotype showed a trend towards longer median progression-free survival (PFS), reaching 86% (p = 0.046).
• Patients with the 4R/4R genotype had a significantly shorter median PFS of 40.4 months (p = 0.026).
• The 4R/4R genotype was associated with a 2.049 times higher risk of shorter PFS (p = 0.009).

Conclusions:

• This study reveals the net effect of PER-3 gene polymorphism on PFS in multiple myeloma.
• The PER-3 gene polymorphism, specifically the 4R/4R genotype, significantly impacts progression-free survival in MM patients.
• Findings provide a basis for future research into circadian gene involvement in MM prognosis and treatment.