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. 2024 Jan 1;15(2):526-532.
doi: 10.7150/jca.89271. eCollection 2024.

ALKBH1 rs2267755 C>T polymorphism decreases neuroblastoma risk in Chinese children

Xinxin Zhang  1 , Chunlei Zhou  2 , Yemu Zhao  3 , Changmi Deng  1 , Haiyan Wu  2 , Zhenjian Zhuo  1   4 , Jing He  1
Affiliations

ALKBH1 rs2267755 C>T polymorphism decreases neuroblastoma risk in Chinese children

Xinxin Zhang et al. J Cancer. .

Abstract

Neuroblastoma is a highly malignant extracranial solid tumor in pediatrics. ALKBH1 as a recently discovered DNA N6-methyldeoxyadenosine (6mA) demethylase closely links to tumorigenesis. Whether the ALKBH1 polymorphism contributes to neuroblastoma risk remains unclear. In the present study, we genotyped the ALKBH1 single nucleotide polymorphisms (SNPs) in 402 neuroblastoma patients and 473 healthy controls by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated to evaluate the strength of the association. Our result exhibited that the rs2267755 C>T (CT vs. CC, adjusted OR=0.69, 95% CI=0.50-0.94, P=0.019) is significantly associated with reduced neuroblastoma risk. And its protective effect is particularly significant in children with tumors originating from the retroperitoneal. Combined genotype analysis revealed that carriers with 1-2 protective genotypes are more susceptible to neuroblastoma than those with 3-4 protective genotypes (adjusted OR=0.71, 95% CI=0.53-0.97, P=0.028). Moreover, the rs2267755 C>T is significantly associated with messenger RNA (mRNA) expression of ALKBH1 and three of its surrounding genes, including SNWQ, ADCK1, and RPL21P10. These results suggest that the rs2267755 C>T may be a genetic variant to reduce neuroblastoma risk.

Keywords: ALKBH1; neuroblastoma; polymorphism; susceptibility.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Functional relevance of rs2267755 C>T on gene expression in GTEx Database. rs2267755 C>T significantly reduced ALKBH1 (A) and SNW1 (B) mRNA expression in the thyroid (P=1.1e-5, P=4.8e-5) as well as in ADCK1 (C) and RPL21P10 (D) in the cell-cultured fibroblasts (P=5.4e-20, P=2.9e-6).
Figure 2
Figure 2
The correlation between gene levels and survival probability of neuroblastoma patients.
See this image and copyright information in PMC

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