ALKBH5 gene polymorphisms and Wilms tumor risk in Chinese children: A five-center case-control study
ALKBH5 gene polymorphisms and Wilms tumor risk in Chinese children: A five-center case-control study
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中国儿童ALKBH5基因多态性与肾母细胞瘤风险：五中心病例对照研究
DOI：
10.1002/jcla.23251
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发表时间：
2020-02-24
影响因子：
2.7
通讯作者：
Zhuo, Zhenjian
中科院分区：
文献类型：
--
作者：
Hua, Rui-Xi;Liu, Jiabin;Zhuo, Zhenjian
背景 肾母细胞瘤是一种在遗传原因不明的儿童中经常被诊断出的肾癌。 N6-甲基腺苷 (m(6)A) 修饰基因在肿瘤发生中发挥关键作用。然而，m(6)A 修饰基因的遗传变异是否易患肾母细胞瘤仍不清楚。 ALKBH5（AlkB 同源物 5）是 m(6)A 修饰基因的重要成员，编码具有逆转 m(6)A RNA 甲基化功能的去甲基化酶。 方法在此，我们在大型多中心评估了 m(6)A 修饰基因 ALKBH5 中的单核苷酸多态性 (SNP) 与肾母细胞瘤易感性之间的关联 病例对照研究。采用 TaqMan 对 414 例肾母细胞瘤病例和 1199 名健康对照者进行了 ALKBH5 rs1378602 和 rs8400 多态性基因分型。结果未发现这两种多态性与肾母细胞瘤风险之间存在显着关联。此外，与仅风险基因型相比，1、2和1-2保护性基因型（rs1378602 AG/AA或rs8400 GG）并未显着降低肾母细胞瘤风险。分层分析显示，rs1378602 AG/AA 基因型与临床 I 期疾病儿童的肾母细胞瘤风险降低之间存在显着关系 [调整后的比值比 (OR) = 0.56，95% 置信区间 (CI) = 0.32-0.98，P = 0.042]。与不存在保护性基因型相比，1-2 种保护性基因型的存在与年龄大于 18 个月的亚组中肾母细胞瘤风险降低相关（调整后 OR = 0.74，95% CI = 0.56-0.98，P = 0.035）。 结论 总的来说，我们的结果表明 ALKBH5 SNP 可能对肾母细胞瘤的易感性产生微弱影响。这一发现增加了对 m(6)A 基因在肾母细胞瘤发生中作用的理解。
Background Wilms tumor is a frequently diagnosed renal cancer among children with unclear genetic causes. N6-methyladenosine (m(6)A) modification genes play critical roles in tumorigenesis. However, whether genetic variations of m(6)A modification genes predispose to Wilms tumor remain unclear. ALKBH5 (AlkB homolog 5), a crucial member of m(6)A modification genes, encodes a demethylase that functions to reverse m(6)A RNA methylation.Methods Herein, we evaluated the association of single nucleotide polymorphisms (SNPs) in the m(6)A modification gene ALKBH5 and Wilms tumor susceptibility in a large multi-center case-control study. A total of 414 Wilms tumor cases and 1199 healthy controls were genotyped for ALKBH5 rs1378602 and rs8400 polymorphisms by TaqMan.Results No significant association was detected between these two polymorphisms and Wilms tumor risk. Moreover, 1, 2, and 1-2 protective genotypes (rs1378602 AG/AA or rs8400 GG) did not significantly reduce Wilms tumor risk, compared with risk genotypes only. Stratification analysis revealed a significant relationship between rs1378602 AG/AA genotypes and decreased Wilms tumor risk in children in clinical stage I diseases [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.32-0.98, P = .042]. The presence of 1-2 protective genotypes was correlated with decreased Wilms tumor risk in subgroups of age > 18 months, when compared to the absence of protective genotypes (adjusted OR = 0.74, 95% CI = 0.56-0.98, P = .035).Conclusion Collectively, our results demonstrate that ALKBH5 SNPs may exert a weak influence on susceptibility to Wilms tumor. This finding increases the understanding of the role of the m(6)A gene in tumorigenesis of Wilms tumor.