METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children

BMC Cancer

Jinhong Zhu¹  Huizhu Zhang²  Haixia Zhou³  Suhong Li⁴  Rui-Xi Hua⁵  Guochang Liu⁵  Jing He⁵  Wei Jia⁵  Huimin Xia⁵  Wen Fu⁵  Zhenjian Zhuo⁵  Jiao Zhang⁶  Jiwen Cheng⁷  Huiran Lin⁸ 

[1] Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, 150040, Harbin, Heilongjiang, China;Department of Gynaecology and Obstetrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, Guangdong, China;Department of Hematology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325027, Wenzhou, Zhejiang, China;Department of Pathology, Children Hospital and Women Health Center of Shanxi, Shannxi, 030013, Taiyuan, China;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, 510623, Guangzhou, Guangdong, China;Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China;Department of Pediatric Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, 710004, Xi’an, Shaanxi, China;Faculty of Medicine, Macau University of Science and Technology, 999078, Macau, China;

关键词: Wilms tumor;    Risk;    METTL14;    Polymorphism;    Case-control study;   

DOI  :  10.1186/s12885-021-09019-5

来源: Springer

【 摘 要 】

BackgroundWilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m6A) 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.MethodsA total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay.ResultAmong 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.ConclusionsCollectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.

【 授权许可】

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