Elwafa Reham Abdel Haleem Abo, Bordiny Magdy El, Salama Mostafa, Fawzy Amira, Omar Omneya Magdy
Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Pediatr Blood Cancer. 2023 Dec;70(12):e30678. doi: 10.1002/pbc.30678. Epub 2023 Sep 20.
Cyclin D2 (CCND2) is a crucial player in cell cycle regulation. CCND2 polymorphisms contribute to cancer predisposition.
To evaluate the association of CCND2 rs3217927 single nucleotide polymorphisms (SNP) and its expression levels with acute lymphoblastic leukemia (ALL) susceptibility in Egyptian children and its potential prognostic role.
The 5' nuclease allelic discrimination assay was used to evaluate the frequency of CCND2 rs3217927 SNP in 80 newly diagnosed children with ALL and 80 age- and sex-matched controls. CCND2 relative expression levels were determined by real-time quantitative polymerase chain reaction.
The genotype analysis revealed that the GG genotype and G allele were significantly more prevalent among ALL patients than controls (p ˂ .001). Regression analysis demonstrated that Egyptian children carrying only one G allele had about 31-fold increased risk to develop ALL compared to A allele carriers. CCND2 was overexpressed in ALL patients compared to controls (p < .001). The CCND2 overexpression was associated with the GG genotype and G allele (p < .001). Furthermore, G allele was an independent negative prognostic marker for central nervous system (CNS) involvement (odds ratio [OR] = 4.676; 95% confidence interval [CI]: 1.2-18.6), risk stratification (OR = 38; 95% CI: 7.7-188.2), and chemoresistance (OR = 9.864; 95% CI: 5.6-70.3) in ALL patients.
G allele of CCND2 rs3217927 SNP might be associated with increased risk for ALL in Egyptian children besides being an independent negative prognostic marker for their risk stratification and therapeutic outcome. CCND2 rs3217927 SNP genotyping might be used to demarcate ALL patients with aggressive disease phenotypes who may be candidate for alternative targeted therapeutic strategies.
细胞周期蛋白D2（CCND2）是细胞周期调控中的关键因子。CCND2基因多态性与癌症易感性相关。
评估埃及儿童中CCND2 rs3217927单核苷酸多态性（SNP）及其表达水平与急性淋巴细胞白血病（ALL）易感性的关联及其潜在的预后作用。
采用5'核酸酶等位基因鉴别分析法评估80例新诊断的ALL儿童及80例年龄和性别匹配的对照中CCND2 rs3217927 SNP的频率。通过实时定量聚合酶链反应测定CCND2相对表达水平。
基因型分析显示，ALL患者中GG基因型和G等位基因的频率显著高于对照组（p＜0.001）。回归分析表明，与携带A等位基因的埃及儿童相比，仅携带一个G等位基因的儿童患ALL的风险增加约31倍。与对照组相比，ALL患者中CCND2表达上调（p＜0.001）。CCND2的过表达与GG基因型和G等位基因相关（p＜0.001）。此外，G等位基因是ALL患者中枢神经系统（CNS）受累（优势比[OR]=4.676；95%置信区间[CI]：1.2 - 18.6）、风险分层（OR = 38；95% CI：7.7 - 188.2）和化疗耐药（OR = 9.864；95% CI：5.6 - 70.3）的独立阴性预后标志物。
CCND2 rs3217927 SNP的G等位基因可能与埃及儿童ALL风险增加相关，并且是其风险分层和治疗结果的独立阴性预后标志物。CCND2 rs3217927 SNP基因分型可用于区分具有侵袭性疾病表型的ALL患者，这些患者可能是替代靶向治疗策略的候选者。
