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, 9 Jinsui Road, Guangzhou, 510623, Guangdong, China.
Department of Gynaecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.
BMC Cancer. 2021 Dec 4;21(1):1294. doi: 10.1186/s12885-021-09019-5.
Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (mA) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility.
A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay.
Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0-4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes.
Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.
Wilms 瘤是一种高度遗传性恶性肿瘤。异常的 METTL14 是 N6-甲基腺苷(mA)甲基转移酶的关键组成部分，参与了致癌过程。METTL14 基因内遗传变异与 Wilms 瘤易感性之间的关系仍有待充分阐明。我们旨在评估该基因内的变异是否与 Wilms 瘤易感性有关。
共分析了 403 例患者和 1198 例对照。采用 TaqMan 基因分型检测 METTL14 基因型。
在所分析的 5 个 SNP 中，rs1064034 T > A 和 rs298982 G > A 与 Wilms 瘤易感性降低显著相关。此外，联合分析显示，与 0-4 种保护性基因型相比，五种保护性基因型的组合对 Wilms 瘤具有更显著的保护作用，OR 为 0.69。分层分析进一步确定了 rs1064034 T > A、rs298982 G > A 和联合五种保护性基因型在特定亚组中的保护作用。上述显著相关性通过单体型分析和假阳性报告概率分析进一步验证。初步的机制探索表明，rs1064034 T > A 和 rs298982 G > A 与周围基因的表达和剪接事件相关。
综上所述，我们的结果表明，METTL14 基因 SNP 可能是 Wilms 瘤发生的遗传修饰因子。
