NF-κB1 -94del/del ATTG polymorphic variant maintains CLL at an early, mildest stage
| Autor: | Dariusz Wołowiec, Anna Jonkisz, Edyta Pawlak, Katarzyna Bogunia-Kubik, Iwona Bil-Lula, Andrzej Tukiendorf, Iwona Urbanowicz, Barbara Wysoczańska, Piotr Łacina, Wiesława Nahaczewska |
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| Rok vydání: | 2021 |
| Předmět: |
Genotype
Chronic lymphocytic leukemia Medicine (miscellaneous) Disease General Biochemistry Genetics and Molecular Biology law.invention law Polymorphism (computer science) hemic and lymphatic diseases Internal Medicine Medicine Humans Pharmacology (medical) Genetic Predisposition to Disease Allele Genetics (clinical) Polymerase chain reaction Polymorphism Genetic business.industry Promoter medicine.disease Phenotype Leukemia Lymphocytic Chronic B-Cell Case-Control Studies Reviews and References (medical) Cancer research Gene polymorphism business |
| Zdroj: | Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 30(5) |
| ISSN: | 1899-5276 |
| Popis: | BACKGROUND NF-κB is an essential player in cancer biology, especially in tumor development, due to its constitutive activation, and because a four-base deletion (ATTG) in the NF-κB1 promoter region at site -94, alters mRNA stability and regulates translation efficiency. This polymorphism is a good candidate risk marker and modulator of clinical course in chronic lymphocytic leukemia (CLL). As the effect of this NF-κB1 gene polymorphism has not been studied in patients with CLL so far, the present study was undertaken to find out whether the NF-κB1 promoter -94 ins/del ATTG polymorphism might be an essential genetic risk factor and/or modulatory disease player associated with CLL. OBJECTIVES The NF-κB1 -94 ins/del ATTG (rs28362491) polymorphism was investigated as a potential CLL susceptibility and progression factor, along with demonstration of potential modulation of the stage of clinical disease based on Rai classification. MATERIAL AND METHODS The associations of NF-κB1 -94 ins/del ATTG polymorphism with CLL and its clinical manifestation in 282 Polish individuals, including 156 CLL patients, were analyzed using polymerase chain reaction (PCR) with primers including a labeled forward primer, followed by capillary electrophoresis. RESULTS A higher occurrence of the del/del homozygosity was observed among patients when compared to controls, resulting in an increase in CLL risk of more than twofold in patients carrying this homozygous genotype (OR = 2.23, p = 0.02, 95% CI = 1.14-4.37). Moreover, the del/del-positive patients more frequently presented the less aggressive disease phenotype (Rai 0), suggesting a low probability of progression to more advanced disease. CONCLUSIONS The NF-κB1 -94 del/del genetic variant, although associated with increased risk of CLL disease, may be associated with maintenance of disease severity in the early, mildest stage. The likelihood of disease progression may increase as the frequency of wild-type (insertion) alleles for this polymorphism increases. |
| Databáze: | OpenAIRE |
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