Mengzhen Zhang, Wenli Zhang, Chunlei Zhou, Jiaming Chang, Jiabin Liu, Lei Lin, Xinxin Zhang, Liping Chen, Jing He, Baowei Han
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Logistic regression was used to assess odds ratios (ORs) and 95% confidence intervals (CIs), while stratification analysis and expression quantitative trait locus (eQTL) analysis were used to examine subgroup-specific effects and regulatory impacts. Additionally, clinical correlation analysis and survival analysis were performed on neuroblastoma datasets used to evaluate. The rs7074891 TC/CC genotype reduced neuroblastoma risk (adjusted OR = 0.75, 95% CI = 0.57–0.98, <i>p</i> = 0.036), especially in children aged ≤ 18 months and those with mediastinal-origin tumours. Conversely, the rs10904887 CC (adjusted OR = 1.73, 95% CI = 1.27–2.38, <i>p</i> = 0.0006) and rs2273734 TT genotypes (adjusted OR = 1.80, 95% CI = 1.09–2.97, <i>p</i> = 0.023) were associated with increased risk, with distinct subgroup-specific effects. Combined 1–3 risk genotypes further confirmed increased susceptibility (adjusted OR = 1.81, 95% CI = 1.38–2.37, <i>p</i> < 0.0001), particularly in males and older children. eQTL analysis revealed that the rs7074891 C and rs10904887 C alleles increased <i>TRDMT1</i> expression, whereas the rs2273734 T allele decreased it. Elevated <i>TRDMT1</i> expression was correlated with poor prognosis and high-risk clinical features. <i>TRDMT1</i> polymorphisms are significantly associated with neuroblastoma susceptibility, providing insights into their genetic and epigenetic mechanisms and potential as biomarkers and therapeutic targets.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70848","citationCount":"0","resultStr":"{\"title\":\"Association of TRDMT1 Gene Polymorphisms With Neuroblastoma Susceptibility: Insights From a Case–Control Study\",\"authors\":\"Mengzhen Zhang, Wenli Zhang, Chunlei Zhou, Jiaming Chang, Jiabin Liu, Lei Lin, Xinxin Zhang, Liping Chen, Jing He, Baowei Han\",\"doi\":\"10.1111/jcmm.70848\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Neuroblastoma is the most common extracranial solid tumour in children, and genetic susceptibility plays a crucial role in its development. The impact of tRNA Dimethyltransferase 1 (TRDMT1), a primary methyltransferase catalysing 5-methylcytosine (m5C) RNA modification, on neuroblastoma susceptibility remains unexplored. We conducted a case–control study involving 402 neuroblastoma patients and 473 controls from Jiangsu, China. <i>TRDMT1</i> polymorphisms (rs7074891 T>C, rs10904887 T>C and rs2273734 C>T) were genotyped via the TaqMan assay. Logistic regression was used to assess odds ratios (ORs) and 95% confidence intervals (CIs), while stratification analysis and expression quantitative trait locus (eQTL) analysis were used to examine subgroup-specific effects and regulatory impacts. Additionally, clinical correlation analysis and survival analysis were performed on neuroblastoma datasets used to evaluate. The rs7074891 TC/CC genotype reduced neuroblastoma risk (adjusted OR = 0.75, 95% CI = 0.57–0.98, <i>p</i> = 0.036), especially in children aged ≤ 18 months and those with mediastinal-origin tumours. 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引用次数: 0
摘要
神经母细胞瘤是儿童最常见的颅外实体瘤，遗传易感性在其发展中起着至关重要的作用。tRNA二甲基转移酶1 （TRDMT1）是一种催化5-甲基胞嘧啶（m5C） RNA修饰的初级甲基转移酶，其对神经母细胞瘤易感性的影响尚不清楚。我们进行了一项病例对照研究，涉及来自中国江苏的402例神经母细胞瘤患者和473例对照。TRDMT1多态性（rs7074891 T>C、rs10904887 T>；C和rs2273734 C>；T）通过TaqMan法进行基因分型。采用Logistic回归评估优势比（ORs）和95%置信区间（CIs），采用分层分析和表达数量性状位点（eQTL）分析检查亚群特异性效应和调控影响。此外，对用于评估的神经母细胞瘤数据集进行临床相关性分析和生存分析。rs7074891 TC/CC基因型降低了神经母细胞瘤的风险（调整后OR = 0.75, 95% CI = 0.57-0.98, p = 0.036），尤其是年龄≤18个月的儿童和纵隔源性肿瘤患者。相反，rs10904887 CC（校正OR = 1.73, 95% CI = 1.27-2.38, p = 0.0006）和rs2273734 TT基因型（校正OR = 1.80, 95% CI = 1.09-2.97, p = 0.023）与风险增加相关，具有明显的亚组特异性效应。合并1-3个危险基因型进一步证实易感性增加（调整后OR = 1.81, 95% CI = 1.38-2.37, p < 0.0001），尤其是男性和年龄较大的儿童。eQTL分析显示，rs7074891 C和rs10904887 C等位基因增加了TRDMT1的表达，而rs2273734 T等位基因降低了TRDMT1的表达。TRDMT1表达升高与预后不良及高危临床特征相关。TRDMT1多态性与神经母细胞瘤易感性显著相关，为其遗传和表观遗传机制以及作为生物标志物和治疗靶点的潜力提供了新的见解。
Association of TRDMT1 Gene Polymorphisms With Neuroblastoma Susceptibility: Insights From a Case–Control Study
Neuroblastoma is the most common extracranial solid tumour in children, and genetic susceptibility plays a crucial role in its development. The impact of tRNA Dimethyltransferase 1 (TRDMT1), a primary methyltransferase catalysing 5-methylcytosine (m5C) RNA modification, on neuroblastoma susceptibility remains unexplored. We conducted a case–control study involving 402 neuroblastoma patients and 473 controls from Jiangsu, China. TRDMT1 polymorphisms (rs7074891 T>C, rs10904887 T>C and rs2273734 C>T) were genotyped via the TaqMan assay. Logistic regression was used to assess odds ratios (ORs) and 95% confidence intervals (CIs), while stratification analysis and expression quantitative trait locus (eQTL) analysis were used to examine subgroup-specific effects and regulatory impacts. Additionally, clinical correlation analysis and survival analysis were performed on neuroblastoma datasets used to evaluate. The rs7074891 TC/CC genotype reduced neuroblastoma risk (adjusted OR = 0.75, 95% CI = 0.57–0.98, p = 0.036), especially in children aged ≤ 18 months and those with mediastinal-origin tumours. Conversely, the rs10904887 CC (adjusted OR = 1.73, 95% CI = 1.27–2.38, p = 0.0006) and rs2273734 TT genotypes (adjusted OR = 1.80, 95% CI = 1.09–2.97, p = 0.023) were associated with increased risk, with distinct subgroup-specific effects. Combined 1–3 risk genotypes further confirmed increased susceptibility (adjusted OR = 1.81, 95% CI = 1.38–2.37, p < 0.0001), particularly in males and older children. eQTL analysis revealed that the rs7074891 C and rs10904887 C alleles increased TRDMT1 expression, whereas the rs2273734 T allele decreased it. Elevated TRDMT1 expression was correlated with poor prognosis and high-risk clinical features. TRDMT1 polymorphisms are significantly associated with neuroblastoma susceptibility, providing insights into their genetic and epigenetic mechanisms and potential as biomarkers and therapeutic targets.
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