Glioma is the most common malignant brain tumor in children. Hox transcription antisense intergenic RNA (HOTAIR) has been shown to promote cancers. However, the role of genetic variation of HOTAIR gene on glioma susceptibility has not been fully elucidated. We aimed to evaluate whether HOTAIR gene single nucleotide polymorphisms (SNPs) are associated with susceptibility to glioma.

The trial included a total of 171 glioma patients and 228 non-glioma controls from Chinese children. Genotyping of HOTAIR gene was evaluated by TaqMan. The strength of the association between HOTAIR gene polymorphism (rs920778 A > G, rs4759314 A > G, rs1899663 C > A) and glioma susceptibility was assessed using odds ratios and 95% confidence intervals. Stratified analysis was further conducted.

Of the three SNPs analyzed, the rs920778 variant and the rs1899663 variant were associated with increased glioma susceptibility. In addition, the combination of two risk genotypes (OR = 1.63, P = 0.028) and one to three risk genotypes (OR = 1.58, P = 0.027) showed a significantly higher increase in glioma susceptibility than zero risk genotypes. These two SNPs (rs920778 A > G, rs1899663 C > A) were significantly associated with increased glioma susceptibility in certain subgroups in stratified analysis. Similar results were found in stratified analyses for one to three risk genotypes compared with zero risk genotypes. Splice quantitative trait loci (sQTLs) indicated rs920778 A > G and rs1899663 C > A are associated with splicing events in certain genes (HOTAIR, HOXC5, HOXC10, HOXC6, and HOXC4).

Overall, our results suggest that some HOTAIR SNPs are associated with increased glioma susceptibility.

Glioma is one of the central nervous system (CNS) tumors in children, accounting for 80% of malignant brain tumors. Nucleotide excision repair (NER) is a vital pathway during DNA damage repair progression. Xeroderma pigmentosum group D (XPD) or excision repair cross‐complementing group 2 (ERCC2) is a critical factor in the NER pathway, playing an indispensable role in the DNA repair process. Therefore, the genetic variants in XPD may be associated with carcinogenesis induced by defects in DNA repair.

We are the first to conduct a multi‐center case‐control study to investigate the correlation between XPD gene polymorphisms and pediatric glioma risk. We chose three single nucleotide polymorphisms and genotyped them using the TaqMan assay.

Although there is no significant association of these genetic variations with glioma susceptibility, the stratified analysis revealed that in the subtype of astrocytic tumors, the rs13181 TG/GG genotype enhanced glioma risk than the TT genotype, and carriers with two to three genotypes also elevated the tumor risk than 0‐1 genotypes.

In conclusion, our findings provided an insight into the impact of XPD genetic variants on glioma risk.