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
Affiliations
Zhenjian Zhuo
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
Rui-Xi Hua
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
Huizhu Zhang
Department of Gynaecology and Obstetrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University
Huiran Lin
Faculty of Medicine, Macau University of Science and Technology
Wen Fu
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
Jinhong Zhu
Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital
Jiwen Cheng
Department of Pediatric Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University
Jiao Zhang
Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University
Suhong Li
Department of Pathology, Children Hospital and Women Health Center of Shanxi
Haixia Zhou
Department of Hematology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University
Huimin Xia
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
Guochang Liu
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
Wei Jia
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
Jing He
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
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.
