Rui Gang, Cheng Ying, Gao Qun
Pediatric Oncologic Surgery, Anhui Children's Hospital, Hefei, 230051, China.
School of Clinical Medicine, Anhui Medical University, Hefei, 230000, China.
Discov Oncol. 2025 Aug 23;16(1):1601. doi: 10.1007/s12672-025-03336-y.
The causal relationship between interleukin-7 levels and neuroblastoma risk remains unclear, and optimal radiation therapy timing lacks definitive evidence. This study investigated causal associations using Mendelian randomization while examining radiation therapy timing effects.
We conducted two-sample Mendelian randomization analysis using GWAS summary statistics for interleukin-7 levels and neuroblastoma with three SNPs as instrumental variables. Multiple MRmethods included inverse variance weighted (IVW), MR-Egger, weighted median, and mode approaches. Additionally, 1,007 neuroblastoma patients from SEER database (2000-2018) were analyzed comparing preoperative (n = 416) versus postoperative (n = 591) radiation therapy using propensity score matching and Cox regression models.
Mendelian randomization revealed significant positive causal association between elevated interleukin-7 levels and increased neuroblastoma risk. The IVW method showed higher interleukin-7 levels associated with 3.6-fold increased odds (OR = 3.585, 95% CI: 1.216-10.575, p = 0.021). In clinical analysis, preoperative radiation demonstrated superior survival outcomes with 27% mortality reduction (HR = 0.73, 95% CI: 0.55-0.97, p = 0.031). Subgroup analysis revealed significant racial differences, with White patients deriving greatest benefit from preoperative radiation (HR = 0.57, 95% CI: 0.42-0.78, p < 0.001).
This study provides evidence for causal relationship between interleukin-7 levels and neuroblastoma risk, suggesting inflammatory pathways' role in pathogenesis.
白细胞介素-7水平与神经母细胞瘤风险之间的因果关系仍不明确，且最佳放疗时机缺乏确凿证据。本研究采用孟德尔随机化方法调查因果关联，同时研究放疗时机的影响。
我们使用全基因组关联研究（GWAS）汇总统计数据，以三个单核苷酸多态性（SNP）作为工具变量，对白细胞介素-7水平和神经母细胞瘤进行两样本孟德尔随机化分析。多种孟德尔随机化方法包括逆方差加权法（IVW）、MR-Egger法、加权中位数法和众数法。此外，我们分析了监测、流行病学与最终结果（SEER）数据库（2000 - 2018年）中的1007例神经母细胞瘤患者，采用倾向得分匹配和Cox回归模型比较术前放疗（n = 416）与术后放疗（n = 591）的情况。
孟德尔随机化显示白细胞介素-7水平升高与神经母细胞瘤风险增加之间存在显著的正因果关联。IVW方法显示白细胞介素-7水平较高与患病几率增加3.6倍相关（比值比[OR]=3.585，95%置信区间[CI]：1.216 - 10.575，p = 0.021）。在临床分析中，术前放疗显示出更好的生存结果，死亡率降低27%（风险比[HR]=0.73，95% CI：0.55 - 0.97，p = 0.031）。亚组分析显示存在显著的种族差异，白人患者从术前放疗中获益最大（HR = 0.57，95% CI：0.42 - 0.78，p < 0.001）。
本研究为白细胞介素-7水平与神经母细胞瘤风险之间的因果关系提供了证据，表明炎症途径在发病机制中的作用。
