Genetic variants of mA modification genes and the risk of neuroblastoma: novel insights from a Chinese case-control study.

BACKGROUND

The N-adenosine methylation (mA) modification plays a significant role in various cancers. However, the functions of mA modification genes and their variants in neuroblastoma remain to be elucidated.

METHODS

We conducted a case-control study involving 402 neuroblastoma patients and 473 cancer-free controls from China via the TaqMan genotyping method to evaluate mA modification gene polymorphisms. Multivariate logistic regression analysis was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Additionally, expression quantitative trait locus (eQTL) analysis utilizing the Genotype-Tissue Expression database was performed to investigate the impacts of significant polymorphisms on gene expression. The relationships between gene expression and the risk and prognosis of neuroblastoma patients were further examined via publicly available datasets by using the R2 platform.

RESULTS

We found that TRMT10C rs4618204 C > T significantly decreased neuroblastoma risk (CT/TT vs. CC: adjusted OR = 0.74, 95% CI = 0.56-0.97, P = 0.030). Moreover, polymorphisms of the TRMT10C (rs3762735), TRMT6 (rs451571 and rs236110), and ALKBH3 (rs10768993 and rs2292889) genes were associated with neuroblastoma risk in specific subgroups. Complete linkage disequilibrium and eQTL analysis revealed a significant association between rs4618204 C > T and reduced expression of the TRMT10C gene. Additionally, higher expression levels of the TRMT10C gene were observed to be linked to increased risk, malignancy, and poorer prognosis in neuroblastoma patients.

CONCLUSIONS

TRMT10C rs4618204 C > T was demonstrated to be significantly associated with an increased risk of neuroblastoma and may serve as a potential molecular marker for early diagnosis. Further studies are warranted to fully elucidate the specific molecular mechanisms involved in this effect.

CLINICAL TRIAL NUMBER

Not applicable.