Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan, 030013 Shannxi, China.
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong 510623, Guangzhou, China.
Gene. 2020 Feb 15;727:144262. doi: 10.1016/j.gene.2019.144262. Epub 2019 Nov 21.
Neuroblastoma is an extracranial solid tumor that mainly occurs in childhood. Mutations of NRAS gene have been described in several cancers. However, whether NRAS gene polymorphisms can predict the risk of neuroblastoma have not been investigated. We hypothesized that variations of NRAS gene contribute to neuroblastoma predisposition. Therefore, we conducted a multi-center case-control study using 263 cases and 715 controls to examine the association of NRAS gene rs2273267 A>T polymorphism and neuroblastoma risk. We calculated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the strength of the associations. Relative to those with AA genotype, subjects with AT/TT genotype had reduced neuroblastoma risk (adjusted OR = 0.72, 95% CI = 0.54-0.96, P = 0.024). Stratified analysis revealed that rs2273267 AT/TT carriers were less likely to develop neuroblastoma for patients with tumor originating from the adrenal gland (adjusted OR = 0.67, 95% CI = 0.45-0.99, P = 0.047) and clinical stages III + IV (adjusted OR = 0.57, 95% CI = 0.36-0.90, P = 0.015). Our findings underline the likely importance of NRAS gene rs2273267 A>T in the risk of neuroblastoma. Further independent case-control studies with functional analysis are needed to verify the role of NRAS gene rs2273267 A>T polymorphism in the risk of neuroblastoma.
神经母细胞瘤是一种主要发生在儿童期的颅外实体瘤。NRAS 基因的突变已在几种癌症中被描述。然而，NRAS 基因多态性是否可以预测神经母细胞瘤的风险尚未被研究。我们假设 NRAS 基因的变异导致神经母细胞瘤易感性。因此，我们进行了一项多中心病例对照研究，共纳入 263 例病例和 715 例对照，以检验 NRAS 基因 rs2273267A>T 多态性与神经母细胞瘤风险之间的关联。我们计算了比值比（ORs）及其对应的 95%置信区间（CIs），以评估关联的强度。与 AA 基因型相比，AT/TT 基因型的个体患神经母细胞瘤的风险降低（调整 OR=0.72，95%CI=0.54-0.96，P=0.024）。分层分析显示，对于起源于肾上腺的肿瘤患者（调整 OR=0.67，95%CI=0.45-0.99，P=0.047）和临床分期 III+IV 期（调整 OR=0.57，95%CI=0.36-0.90，P=0.015），rs2273267 AT/TT 携带者患神经母细胞瘤的风险较低。我们的研究结果强调了 NRAS 基因 rs2273267A>T 在神经母细胞瘤风险中的重要性。需要进一步进行独立的病例对照研究，并结合功能分析，以验证 NRAS 基因 rs2273267A>T 多态性在神经母细胞瘤风险中的作用。
