Genetic variants of m7G modification genes influence neuroblastoma susceptibility
Jiabin Liu,
Changmi Deng,
Huiran Lin,
Xinxin Zhang,
Jinhong Zhu,
Chunlei Zhou,
Haiyan Wu,
Jing He
Affiliations
Jiabin 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, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, Guangdong, China
Changmi Deng
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, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, Guangdong, China
Huiran Lin
Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China
Xinxin Zhang
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, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, Guangdong, China
Jinhong Zhu
Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China
Chunlei Zhou
Department of Pathology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China
Haiyan Wu
Department of Pathology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China
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, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, Guangdong, China; Corresponding author. 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, Guangdong Provincial Clinical Research Center for Child Health, 9 Jinsui Road, Guangzhou 510623, Guangdong, China.
Objective: Neuroblastoma is a life-threatening pediatric solid tumor whose etiology remains unclear. N7-methylguanosine (m7G) is one of the most important epigenetic modifications of RNA, which plays a crucial role in tumorigenesis. The m7G-mediated genes METTL1 and WDR4 also have been reported to be dysregulated in various cancers. However, the implications of METTL1 and WDR4 in neuroblastoma have not been clarified. Methods: Given the oncogenic potential of m7G modification, we performed a case-control study to assess the association of METTL1 and WDR4 genes polymorphisms with neuroblastoma risk in a Chinese population consisting of 402 cases and 473 controls. Odds ratios (ORs) and 95 % confidence intervals (CIs) were applied to evaluate the associations between studied polymorphisms and neuroblastoma risk. The adjusted odds ratio (AOR) was adjusted for age and gender. Results: Overall, four polymorphisms were significantly associated with neuroblastoma risk, including METTL1 rs2291617 (recessive model: adjusted OR = 1.59, 95 % CI = 1.08–2.34, P = 0.019), WDR4 rs2156316 (dominant model: adjusted OR = 0.74, 95 % CI = 0.57–0.97, P = 0.028), WDR4 rs6586250 (dominant model: adjusted OR = 0.59, 95 % CI = 0.42–0.84, P = 0.004) and WDR4 rs15736 (dominant model: adjusted OR = 0.60, 95 % CI = 0.42–0.85, P = 0.004). Stratified analysis showed stronger correlations between significant polymorphisms and neuroblastoma risk among subgroups divided by age, gender, tumor origin, and clinical stage. Furthermore, expression quantitative trait loci (eQTL) analysis revealed that significant polymorphisms were associated with the expression of the adjacent genes. Conclusions: Our study indicated that four polymorphisms in m7G-mediated genes contribute to neuroblastoma susceptibility in the eastern Chinese population. However, our findings should be verified further by large-scale and well-designed studies.
