Causal Relationship Between Galectins With Neuroblastoma: A Mendelian Randomization Study

Galectins are a family of proteins that are involved in various aspects of cancer, including tumor growth, cell migration, invasion, and metastasis. Galectins are subdivided into three families: prototype (such as Gal-1), chimera type (such as Gal-3), and tandem repeat type (such as Gal-9). Despite the evidence linking galectins to the risk of neuroblastoma (NB), the causal association between galectins and NB remains unclear. The primary objective of this study is to clarify the causal effect of galectins (including Gal-1, Gal-3, and Gal-9) on NB risk through a two-sample Mendelian randomization (MR) study. The MR study was performed using summary statistics from extensive genome-wide association studies. Single-nucleotide polymorphisms (SNPs) related to the exposure variables were used as instrumental variables. The primary outcome was NB risk, and the exposure variables included Gal-1, Gal-3, and Gal-9. We chose inverse-variance weighted (IVW), constrained maximum likelihood and model averaging (cML-MA), MR-robust adjusted profile score (MR-RAPS), simple mode, weighted median, and weighted mode as the statistical methods to assess the causal effect; and the IVW method was the primary statistical method. Odds ratio (OR) and 95% confidence interval (CI) were used as the evaluation indices for causality. According to the IVW with fixed-effect results, genetically predicted Gal-9 was associated with an increased risk of NB (OR = 1.639, 95% CI 1.171-2.293, P = 0.004). Similar risk estimates were obtained using cML-MA, MR-RAPS, simple mode, weighted median, and weighted mode. Additionally, the IVW with fixed-effect revealed there was no statistically significant association between Gal-1 and NB (P = 0.605), or between Gal-3 and NB (P = 0.258). No evidence of reverse causality was observed in the MR Steiger test. The results of the leave-one-out sensitivity test confirmed the stability and reliability of the causal effect estimates. This study identified a possible causal association between Gal-9 levels and the risk of NB through a two-sample MR analysis, which might provide preliminary yet insightful findings into the role of Gal-9 in the development of NB. We hope that our findings would promote the exploration of therapeutic strategies for NB.