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Genetically predicted interleukin 7 levels and neuroblastoma risk combined with analysis of radiation therapy timing
Gang Rui1, Ying Cheng2, Qun Gao3
1Pediatric Oncologic Surgery, Anhui Children's Hospital, Hefei, 230051, China.
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.
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