Hares Seddam, Hamizi Kamel, Rahab Hamza, Bounneche Maewa Hibatouallah, Aouidane Souhila, Mansoura Leila, Denni Manel, Mallem Wissem, Belaaloui Ghania
Laboratory of Acquired and Constitutional Genetic Diseases (MAGECA), Faculty of Medicine, Batna 2 University, Batna 05000, Algeria.
Faculty of Nature and Life Sciences, Batna 2 University, Batna 05000, Algeria.
Int J Mol Sci. 2025 Sep 1;26(17):8486. doi: 10.3390/ijms26178486.
The undifferentiated nasopharyngeal cancer (NPC) is a multifactorial disease mainly due to Epstein-Barr Virus (EBV) infection. The transmembrane tyrosine kinase 'EphA2' and the protease 'Furin' are implicated in the EBV entry into epithelial cells and other physiological processes. To gain insights into the association of single-nucleotide polymorphisms (SNPs) rs4702 and rs6603883 ( and genes, respectively) with the risk and prognosis of the NPC, the genotypes of 471 individuals (228 cases and 243 controls) were assessed alongside risk cofactors (sex, tobacco, alcohol, occupation, and recurrent Ear, Nose and Throat infections) and prognosis cofactors (Tumor stage, local invasion, lymph node involvement, and metastasis) using multivariable logistic regression. We found that only the rs4702 AG/GG genotypes were statistically significantly associated with a reduced risk of cancer, both in the overall population and in men (approximately 50% reduction). The rs4702 GG genotype was also associated with a low frequency of local tumor invasion in the whole population (OR = 0.382, = 0.017, co-dominant model, and OR = 0.409, = 0.02, recessive model), but heterozygous women were associated with a higher lymph node involvement (OR = 3.53, = 0.031, co-dominant model, and OR = 3.62, = 0.02, overdominant model). The rs6603883 GG genotype was associated, in the dominant model, with distant metastasis in the whole population (OR = 2.5, = 0.024), with advanced clinical stage in men (OR = 2.22, = 0.034), and with advanced clinical stage and distant metastasis in patients under 49 years (OR = 3.13, = 0.009, and OR = 5.15, = 0.011, respectively). Additionally, men having the rs6603883 GA genotype were associated with lymph node invasion (OR = 2.22, = 0.027, overdominant model). Our study is the first to demonstrate that and germline gene polymorphisms are associated with NPC risk (for rs4702) and prognosis (for both rs4702 and rs6603883), with sex-specific differences. These results need to be replicated and further investigated in other populations.
未分化鼻咽癌（NPC）是一种多因素疾病，主要归因于爱泼斯坦-巴尔病毒（EBV）感染。跨膜酪氨酸激酶“EphA2”和蛋白酶“弗林蛋白酶”与EBV进入上皮细胞及其他生理过程有关。为深入了解单核苷酸多态性（SNP）rs4702和rs6603883（分别位于 和 基因）与NPC风险及预后的关联，我们使用多变量逻辑回归对471名个体（228例病例和243名对照）的基因型以及风险协变量（性别、烟草、酒精、职业和耳鼻喉反复感染）和预后协变量（肿瘤分期、局部侵袭、淋巴结受累和转移）进行了评估。我们发现，仅rs4702的AG/GG基因型在总体人群和男性中均与癌症风险降低具有统计学显著关联（降低约50%）。rs4702的GG基因型在总体人群中也与局部肿瘤侵袭频率较低相关（共显性模型中OR = 0.382， = 0.017；隐性模型中OR = 0.409， = 0.02），但杂合子女性与较高的淋巴结受累相关（共显性模型中OR = 3.53， = 0.031；超显性模型中OR = 3.62， = 0.02）。rs6603883的GG基因型在显性模型中与总体人群的远处转移相关（OR = 2.5， = 0.024），与男性的晚期临床分期相关（OR = 2.22， = 0.034），与49岁以下患者的晚期临床分期和远处转移相关（分别为OR = 3.13， = 0.009；OR = 5.15， = 0.011）。此外，具有rs6603883的GA基因型的男性与淋巴结侵袭相关（超显性模型中OR = 2.22， = 0.027）。我们的研究首次证明 和 种系基因多态性与NPC风险（对于rs4702）和预后（对于rs4702和rs6603883）相关，且存在性别特异性差异。这些结果需要在其他人群中进行重复和进一步研究。
