Department of Clinical Chemistry, Department of Hematology, Wroclaw Medical University, Poland.
Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Poland.
Adv Clin Exp Med. 2021 May;30(5):499-506. doi: 10.17219/acem/128764.
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.
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.
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.
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.
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.
NF-κB 是癌症生物学中的一个重要参与者，尤其是在肿瘤的发展过程中，因为它的组成性激活，以及在 NF-κB1 启动子区域的位置 -94 处存在一个四碱基缺失（ATTG），改变了 mRNA 的稳定性并调节翻译效率。这种多态性是慢性淋巴细胞白血病（CLL）临床病程的一个很好的候选风险标志物和调节剂。由于到目前为止，NF-κB1 基因多态性在 CLL 患者中的作用尚未得到研究，因此本研究旨在确定 NF-κB1 启动子 -94 ins/del ATTG 多态性是否可能是与 CLL 相关的重要遗传风险因素和/或疾病调节因子。
研究 NF-κB1 -94 ins/del ATTG（rs28362491）多态性是否可能是 CLL 的易感性和进展因素，并根据 Rai 分类证明其对临床疾病阶段的潜在调节作用。
使用聚合酶链反应（PCR）和带有标记正向引物的引物，对 282 名波兰个体（包括 156 名 CLL 患者）的 NF-κB1 -94 ins/del ATTG 多态性与 CLL 及其临床表现的相关性进行分析，随后进行毛细管电泳。
与对照组相比，患者中观察到 del/del 纯合性的发生率更高，导致携带这种纯合基因型的患者 CLL 风险增加两倍以上（OR = 2.23，p = 0.02，95%CI = 1.14-4.37）。此外，del/del 阳性患者更频繁地表现出侵袭性较低的疾病表型（Rai 0），表明向更晚期疾病进展的可能性较低。
NF-κB1 -94 del/del 遗传变异虽然与 CLL 疾病的风险增加相关，但可能与疾病在早期、最轻微阶段的严重程度维持有关。随着该多态性野生型（插入）等位基因的频率增加，疾病进展的可能性可能会增加。
