Zhang Ting, Yin Huimin, Guo Jiejie, Chang Jiaming, Li Mengjia, He Jing, Zhou Chunlei
Department of Clinical Laboratory, The First People's Hospital of Wenling, Affiliated Wenling Hospital, Wenzhou Medical University, Taizhou, 317500, Zhejiang, China.
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.
Eur J Pediatr. 2024 Dec 24;184(1):104. doi: 10.1007/s00431-024-05942-4.
Neuroblastoma, " a malignancy originating from neural crest cells, is most commonly diagnosed in children and adolescents. Polymorphisms within the long noncoding RNA (lncRNA) HOXA distal transcript antisense RNA (HOTTIP) are believed to have the capacity to alter an individual's susceptibility to various cancers. This study aimed to investigate the link between HOTTIP gene polymorphisms and neuroblastoma susceptibility. We identified the genotypes of two prevalent polymorphisms (rs3807598 and rs1859168) within the HOTTIP via the TaqMan assay in a cohort comprising 402 individuals diagnosed with neuroblastoma and 473 healthy controls. Logistic regression was used to evaluate the associations between the HOTTIP polymorphisms and the likelihood of neuroblastoma susceptibility. Additionally, the genotype-tissue expression (GTEx) database was used to investigate how these HOTTIP gene variations influence gene expression across different tissues. Our findings demonstrated a significant association between the rs1859168 C > A polymorphism and reduced neuroblastoma susceptibility (CA vs. CC: adjusted odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.40-0.74, P = 0.0001; CA/AA vs. CC: adjusted OR = 0.69, 95% CI = 0.53-0.91, P = 0.010). The additional stratified analysis revealed that the presence of rs1859168 CA/AA or two protective genotypes was associated with a lower susceptibility in specific subgroups, such as older children and girls. Expression quantitative trait locus (eQTL) analysis revealed that the rs1859168 CC genotype was related to high expression of the HOTTIP gene.
We found that HOTTIP gene polymorphisms were associated with a reduced likelihood of neuroblastoma in Chinese children. Further studies with large cohorts and diverse ethnicities are warranted to verify our results.
• Genetic variations can influence neuroblastoma susceptibility. HOTTIP gene polymorphisms may alter an individual's susceptibility to various cancers.
• HOTTIP gene polymorphisms were associated with a reduced risk of neuroblastoma in Chinese children.
神经母细胞瘤是一种起源于神经嵴细胞的恶性肿瘤，最常见于儿童和青少年。长链非编码RNA（lncRNA）HOXA远端转录本反义RNA（HOTTIP）内的多态性被认为有能力改变个体对各种癌症的易感性。本研究旨在调查HOTTIP基因多态性与神经母细胞瘤易感性之间的联系。我们通过TaqMan分析在一个包含402例诊断为神经母细胞瘤的个体和473例健康对照的队列中确定了HOTTIP内两个常见多态性（rs3807598和rs1859168）的基因型。采用逻辑回归评估HOTTIP多态性与神经母细胞瘤易感性可能性之间的关联。此外，利用基因型-组织表达（GTEx）数据库研究这些HOTTIP基因变异如何影响不同组织中的基因表达。我们的研究结果表明，rs1859168 C>A多态性与神经母细胞瘤易感性降低显著相关（CA与CC相比：调整后的比值比（OR）=0.55，95%置信区间（CI）=0.40-0.74，P=0.0001；CA/AA与CC相比：调整后的OR=0.69，95%CI=0.53-0.91，P=0.010）。进一步的分层分析显示，rs1859168 CA/AA或两种保护性基因型的存在与特定亚组（如年龄较大的儿童和女孩）的较低易感性相关。表达数量性状位点（eQTL）分析显示，rs1859168 CC基因型与HOTTIP基因的高表达相关。
我们发现HOTTIP基因多态性与中国儿童神经母细胞瘤发生可能性降低相关。需要进行更大队列和不同种族的进一步研究来验证我们的结果。
• 基因变异可影响神经母细胞瘤易感性。HOTTIP基因多态性可能改变个体对各种癌症的易感性。
• HOTTIP基因多态性与中国儿童神经母细胞瘤风险降低相关。
