METTL14 Gene Polymorphisms Confer Neuroblastoma Susceptibility: An Eight-Center Case-Control Study

Zhenjian Zhuo; Hongting Lu; Jinhong Zhu; Rui-Xi Hua; Yong Li; Zhonghua Yang; Jiao Zhang; Jiwen Cheng; Haixia Zhou; Suhong Li; Li Li; Huimin Xia; Jing He

doi:10.1016/j.omtn.2020.08.009

METTL14 Gene Polymorphisms Confer Neuroblastoma Susceptibility: An Eight-Center Case-Control Study

Mol Ther Nucleic Acids. 2020 Aug 14:22:17-26. doi: 10.1016/j.omtn.2020.08.009. Online ahead of print.

Authors

Zhenjian Zhuo¹, Hongting Lu², Jinhong Zhu³, Rui-Xi Hua¹, Yong Li⁴, Zhonghua Yang⁵, Jiao Zhang⁶, Jiwen Cheng⁷, Haixia Zhou⁸, Suhong Li⁹, Li Li¹⁰, Huimin Xia¹¹, Jing He¹²

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, Guangzhou 510623, Guangdong, China.
² Department of Pediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China.
³ 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 510623, Guangdong, China; Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.
⁴ Department of Pediatric Surgery, Hunan Children's Hospital, Changsha 410004, Hunan, China.
⁵ Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
⁶ Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
⁷ Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, 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 Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China.
¹⁰ Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases, Kunming Children's Hospital, Kunming 650228, Yunnan, China.
¹¹ 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 510623, Guangdong, China. Electronic address: xia-huimin@foxmail.com.
¹² 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 510623, Guangdong, China. Electronic address: hejing198374@gmail.com.

Abstract

Neuroblastoma is the primary cause of cancer death in childhood. METTL14 is tightly linked to cancer. However, whether single-nucleotide polymorphisms (SNPs) in the METTL14 gene could predispose to neuroblastoma susceptibility lacks evidence. With an epidemiology case-control study, associations between METTL14 gene SNPs and overall risk for neuroblastoma were estimated in 898 cases and 1,734 controls. Following that, stratified analysis was performed. Among the five analyzed SNPs, rs298982 G>A and rs62328061 A>G exhibited a significant association with decreased susceptibility to neuroblastoma, whereas the associations with increased neuroblastoma susceptibility were observed for rs9884978 G>A and rs4834698 T>C. Moreover, subjects carrying two to five risk genotypes were more inclined to develop neuroblastoma than those with zero to one risk genotypes. The stratified analysis further demonstrated the protective effect of rs298982 G>A and rs62328061 A>G, as well as the predisposing effect of rs4834698 T>C and two to five risk genotypes, in certain subgroups. Haplotype analysis was performed. Moreover, false-positive report probability analysis validated the reliability of the significant results. The expression quantitative trait locus analysis revealed that rs298982 is correlated with the expression levels of its surrounding genes. Our results suggest that some SNPs in the METTL14 gene are associated with predisposition to neuroblastoma.

Keywords: METTL14; case-control study; m(6)A; neuroblastoma; polymorphism.