Xie Lili, Luo Dongyuan, Chen Xuemei, Zhang Mengzhen, Zhang Wenli, Chang Jiaming, Zhou Haixia, Zhang Xinxin, He Jing, Chen Liping, Zhou Chunlei
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.
Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.
Pediatr Surg Int. 2025 May 5;41(1):130. doi: 10.1007/s00383-025-06025-7.
To evaluate the potential association between single nucleotide polymorphisms in the RAS gene and neuroblastoma risk, we examined four candidate SNPs within this gene.
Our hospital-based case-control study included 402 cases and 473 controls. Four SNPs (rs12587 G > T, rs7973450 A > G, and rs7312175 G > A in KRAS and rs2273267 A > T in NRAS) were genotyped using the TaqMan assay. The association between RAS gene polymorphisms and neuroblastoma susceptibility was assessed through odds ratios and 95% confidence intervals.
None of the four candidate SNPs exhibited a significant attribution to neuroblastoma risk. However, the concurrent presence of 2-3 KRAS risk genotypes significantly conferred an increased susceptibility to neuroblastoma (adjusted odds ratio [AOR] = 2.55, 95% confidence interval [CI] 1.33-4.89; P = 0.005). Further stratified analyses indicated that carriers of the KRAS rs12587 TT genotype tended to be more predisposed to neuroblastoma in males and in the subgroup with tumors originating from other sites. Additionally, the co-occurrence of 2-3 KRAS risk genotypes was found to be linked to an increased neuroblastoma risk in subgroups of individuals older than 18 months, males, tumors originating from retroperitoneum, mediastinum, or other sites, and those with tumors at clinical stage III + IV, respectively.
In summary, a single KRAS gene polymorphism may be weakly associated with an increased risk of childhood neuroblastoma in Jiangsu province, China, while the presence of more KRAS risk genotypes may increase the contribution to the risk of neuroblastoma.
为了评估RAS基因单核苷酸多态性与神经母细胞瘤风险之间的潜在关联，我们检测了该基因内的四个候选单核苷酸多态性。
我们基于医院的病例对照研究纳入了402例病例和473例对照。使用TaqMan分析法对四个单核苷酸多态性（KRAS基因中的rs12587 G＞T、rs7973450 A＞G和rs7312175 G＞A以及NRAS基因中的rs2273267 A＞T）进行基因分型。通过比值比和95%置信区间评估RAS基因多态性与神经母细胞瘤易感性之间的关联。
四个候选单核苷酸多态性均未显示出对神经母细胞瘤风险有显著影响。然而，同时存在2 - 3种KRAS风险基因型显著增加了神经母细胞瘤的易感性（校正比值比[AOR] = 2.55，95%置信区间[CI] 1.33 - 4.89；P = 0.005）。进一步的分层分析表明，KRAS rs12587 TT基因型携带者在男性以及肿瘤起源于其他部位的亚组中更容易患神经母细胞瘤。此外，分别在18个月以上个体、男性、肿瘤起源于腹膜后、纵隔或其他部位以及临床分期为III + IV期肿瘤的亚组中，发现同时存在2 - 3种KRAS风险基因型与神经母细胞瘤风险增加有关。
总之，在中国江苏省，单个KRAS基因多态性可能与儿童神经母细胞瘤风险增加存在弱关联，而更多KRAS风险基因型的存在可能增加对神经母细胞瘤风险的影响。
