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

Xinxin Zhang; Bo Wang; Lei Lin; Chunlei Zhou; Jinhong Zhu; Haiyan Wu; Jing He

doi:10.1016/j.heliyon.2024.e27988

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

Heliyon. 2024 Mar 12;10(6):e27988. doi: 10.1016/j.heliyon.2024.e27988. eCollection 2024 Mar 30.

Authors

Xinxin Zhang¹, Bo Wang², Lei Lin¹, Chunlei Zhou³, Jinhong Zhu⁴, Haiyan Wu³, Jing He¹

Affiliations

¹ Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
² Department of Clinical Laboratory, Qingdao Eighth People's Hospital, Qingdao 266100, Shandong, China.
³ Department of Pathology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China.
⁴ Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.

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: Polymorphism; Susceptibility; TET3; m5C modification; neuroblastoma.