METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children

Zhenjian Zhuo; Rui-Xi Hua; Huizhu Zhang; Huiran Lin; Wen Fu; Jinhong Zhu; Jiwen Cheng; Jiao Zhang; Suhong Li; Haixia Zhou; Huimin Xia; Guochang Liu; Wei Jia; Jing He

doi:10.1186/s12885-021-09019-5

METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children

BMC Cancer. 2021 Dec 4;21(1):1294. doi: 10.1186/s12885-021-09019-5.

Authors

Zhenjian Zhuo^#¹, Rui-Xi Hua^#¹, Huizhu Zhang^#², Huiran Lin³, Wen Fu¹, Jinhong Zhu⁴, Jiwen Cheng⁵, Jiao Zhang⁶, Suhong Li⁷, Haixia Zhou⁸, Huimin Xia¹, Guochang Liu¹, Wei Jia⁹, Jing He¹⁰

Affiliations

¹ 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.
² Department of Gynaecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.
³ Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, China.
⁴ Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin, 150040, Heilongjiang, China.
⁵ Department of Pediatric Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
⁶ Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
⁷ Department of Pathology, Children Hospital and Women Health Center of Shanxi, Shannxi, Taiyuan, 030013, China.
⁸ Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
⁹ 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. jiawei198044@hotmail.com.
¹⁰ 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. hejing198374@gmail.com.

^# Contributed equally.

Abstract

Background: Wilms 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.

Methods: A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay.

Result: 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.

Conclusions: Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.

Keywords: Case-control study; METTL14; Polymorphism; Risk; Wilms tumor.

MeSH terms

Asian People
Case-Control Studies
Child
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Methyltransferases / metabolism*
Polymorphism, Genetic / genetics*
Polymorphism, Single Nucleotide / genetics*
Wilms Tumor / genetics*

Substances

METTL14 protein, human
Methyltransferases