NF-κB1 -94del/del ATTG polymorphic variant maintains CLL at an early, mildest stage.

Area of Science:

• Genetics and Cancer Biology
• Molecular Oncology
• Hematology

Background:

• Nuclear factor-kappa B (NF-κB) is crucial in cancer development, with specific promoter polymorphisms affecting gene expression.
• A four-base deletion (ATTG) in the NF-κB1 promoter (-94 position) influences mRNA stability and translation, potentially impacting cancer risk and progression.
• The NF-κB1 -94 ins/del ATTG polymorphism has not been previously studied in chronic lymphocytic leukemia (CLL).

Purpose of the Study:

• To investigate the NF-κB1 -94 ins/del ATTG polymorphism as a risk factor for CLL susceptibility.
• To assess the polymorphism's role in CLL progression and clinical manifestation based on Rai staging.
• To determine if rs28362491 influences CLL disease severity and progression dynamics.

Main Methods:

• Polymerase chain reaction (PCR) with labeled primers was used to genotype the NF-κB1 -94 ins/del ATTG polymorphism.
• Capillary electrophoresis was employed for precise genotyping of the polymorphism.
• The study analyzed 282 Polish individuals, including 156 patients diagnosed with CLL.

Main Results:

• Homozygosity for the del/del genotype of the NF-κB1 -94 polymorphism was significantly more frequent in CLL patients than controls (OR = 2.23, p = 0.02).
• Patients with the del/del genotype exhibited a more than twofold increased risk of developing CLL.
• Del/del homozygotes were more often diagnosed with early-stage disease (Rai 0), suggesting a less aggressive phenotype.

Conclusions:

• The NF-κB1 -94 del/del variant is associated with an elevated risk of CLL.
• Despite increased risk, the del/del genotype may be linked to maintaining the disease in an early, less severe stage.
• A higher frequency of wild-type (insertion) alleles for this polymorphism might correlate with increased CLL progression likelihood.