TET3 gene rs828867 G>A polymorphism reduces neuroblastoma risk in Chinese children

Abstract

Objective: Neuroblastoma (NB) is a prevalent pediatric tumor originating from primordial neural crest cells. As one of the latest epigenetics investigations focuses, RNA 5-methylcytosine (m5C) is closely related to cancer risk. TET methylcytosine dioxygenase 3 (TET3) is a demethylase for m5C modification. Whether there is an association between TET3 gene polymorphisms and neuroblastoma risk remains unclear. Methods: We conducted an epidemiological study in 402 patients and 473 controls to evaluate the relationship between TET3 gene SNPs (rs7560668 T > C, rs828867 G > A, and rs6546891 A > G) and NB susceptibility. Results: Our results showed that rs828867 G > A significantly reduced NB risk in Chinese children [GA vs. GG, adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.52–0.98, P=0.040; GA/AA vs. GG, adjusted OR = 0.74, 95% CI = 0.55–0.998, P=0.048]. Individuals with 2–3 risk genotypes had a significantly higher NB risk than those with 0–1 risk genotypes (adjusted OR = 1.40, 95% CI = 1.04–1.88, P=0.027). The stratified analysis showed that the rs828867 G > A associated with decreased NB risk is remarkable among children aged >18 months (adjusted OR = 0.67, 95% CI = 0.46–0.96, P=0.029) and patients at clinical III + IV stages (adjusted OR = 0.67, 95% CI = 0.45–0.98, P=0.040). Compared with the 0–1 risk genotype, the concurrence of 2–3 risk genotypes significantly increased NB risk in the following subgroups: children aged >18 months and patients at clinical III + IV stages. GTEx analysis suggested that rs828867 G > A was significantly associated with RP11-287D1.4 and POLE4 mRNA expression. Conclusions: Overall, our results revealed that rs828867 G > A in the TET3 gene is significantly associated with predisposition to NB.

Keywords

• TET3
• Polymorphism
• neuroblastoma
• Susceptibility
• m5C modification