Departamento de Hemato-Oncología, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Ciudad de México 06720, Mexico.
Unidad de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Ciudad de México 06720, Mexico.
Int J Mol Sci. 2024 Oct 1;25(19):10590. doi: 10.3390/ijms251910590.
The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine's increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03-0.393, = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45-5.76, = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068-0.63, = 0.006). Circulating TNF-α serum concentrations were significantly different ( < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival ( = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of genetic polymorphisms to the risk and prognosis of NB.
体外和体内研究的结果表明 TNF-α 具有促肿瘤作用，这种细胞因子的表达增加与某些类型癌症患者的预后不良有关。我们的研究目的是评估 TNF-α 遗传多态性和血清水平与墨西哥神经母细胞瘤患者易感性和预后的可能相关性。我们分别使用 PCR-RFLP 和 ELISA 方法分析这些 SNP 的遗传学和确定血清浓度。-308 G>A 和-238 G>A 多态性基因型在神经母细胞瘤患者和对照组之间的分布有很大差异。SNP rs1800629 GG/GA 基因型与神经母细胞瘤的发病风险降低相关（OR = 0.1，95%CI = 0.03-0.393， = 0.001），而 AA 基因型与神经母细胞瘤的易感性相关（OR = 2.89，95%CI = 1.45-5.76， = 0.003），并与不良组织学和高危神经母细胞瘤相关。rs361525 多态性 GG 基因型与发生神经母细胞瘤的风险较低相关，与 GA 和 AA 基因型相比（OR = 0.2，95%CI = 0.068-0.63， = 0.006）。神经母细胞瘤患者和健康对照组之间的 TNF-α 血清浓度有显著差异（ < 0.001）；然而，我们没有发现分析的 TNF-α 血清水平与 SNP 基因型之间的关系。我们发现 rs1800629AA 基因型与无事件生存时间较低相关（ = 0.026）；rs361525 和 TNF-α 水平与神经母细胞瘤患者的生存无关。我们的结果表明 TNF-α SNP rs1800629 可能是神经母细胞瘤易感性的一个因素。-308 G/A 多态性 AA 基因型可能在促进神经母细胞瘤的发展和与不良组织学、高危肿瘤和较低 EFS 相关的不良预后中起作用。值得注意的是，通过机构间研究进行更大规模的研究，以进一步评估遗传多态性对神经母细胞瘤风险和预后的贡献是很重要的。
