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, China.
Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
J Clin Lab Anal. 2020 Jun;34(6):e23251. doi: 10.1002/jcla.23251. Epub 2020 Feb 24.
Wilms tumor is a frequently diagnosed renal cancer among children with unclear genetic causes. N6-methyladenosine (m A) modification genes play critical roles in tumorigenesis. However, whether genetic variations of m A modification genes predispose to Wilms tumor remain unclear. ALKBH5 (AlkB homolog 5), a crucial member of m A modification genes, encodes a demethylase that functions to reverse m A RNA methylation.
Herein, we evaluated the association of single nucleotide polymorphisms (SNPs) in the m 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.
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).
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 A gene in tumorigenesis of Wilms tumor.
Wilms 肿瘤是儿童中常见的肾部癌症，其病因尚不清楚。N6-甲基腺苷（m A）修饰基因在肿瘤发生中起着关键作用。然而，m A 修饰基因的遗传变异是否易患 Wilms 肿瘤尚不清楚。ALKBH5（AlkB 同源物 5）是 m A 修饰基因的重要成员，其编码的去甲基化酶可逆转 m A RNA 甲基化。
在此，我们在一项大型多中心病例对照研究中评估了 m A 修饰基因 ALKBH5 的单核苷酸多态性（SNP）与 Wilms 肿瘤易感性的关联。通过 TaqMan 对 414 例 Wilms 肿瘤病例和 1199 例健康对照进行 ALKBH5 rs1378602 和 rs8400 多态性的基因分型。
未发现这两个多态性与 Wilms 肿瘤风险之间存在显著关联。此外，与仅携带风险基因型相比，1、2 和 1-2 种保护基因型（rs1378602 AG/AA 或 rs8400 GG）并不能显著降低 Wilms 肿瘤风险。分层分析显示，rs1378602 AG/AA 基因型与临床分期 I 期疾病患儿 Wilms 肿瘤风险降低之间存在显著关系[校正比值比（OR）=0.56，95%置信区间（CI）=0.32-0.98，P=0.042]。当与不存在保护基因型相比，存在 1-2 种保护基因型与 Wilms 肿瘤风险降低相关（校正 OR=0.74，95%CI=0.56-0.98，P=0.035）。
总的来说，我们的研究结果表明 ALKBH5 SNP 可能对 Wilms 肿瘤易感性有微弱影响。这一发现增加了对 m A 基因在 Wilms 肿瘤发生中的作用的理解。
