Genetically predicted interleukin 7 levels and neuroblastoma risk combined with analysis of radiation therapy timing effects.

BACKGROUND

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.

METHODS

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.

RESULTS

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).

RESULTS

This study provides evidence for causal relationship between interleukin-7 levels and neuroblastoma risk, suggesting inflammatory pathways' role in pathogenesis.