YTHDF2 Gene rs3738067 A>G Polymorphism Decreases Neuroblastoma Risk in Chinese Children: Evidence From an Eight-Center Case-Control Study

Huijuan Zeng; Meng Li; Jiabin Liu; Jinhong Zhu; Jiwen Cheng; Yong Li; Jiao Zhang; Zhonghua Yang; Li Li; Haixia Zhou; Suhong Li; Huimin Xia; Yan Zou; Jing He; Tianyou Yang

doi:10.3389/fmed.2021.797195

YTHDF2 Gene rs3738067 A>G Polymorphism Decreases Neuroblastoma Risk in Chinese Children: Evidence From an Eight-Center Case-Control Study

Front Med (Lausanne). 2021 Dec 14:8:797195. doi: 10.3389/fmed.2021.797195. eCollection 2021.

Authors

Huijuan Zeng¹, Meng Li¹, Jiabin Liu¹, Jinhong Zhu², Jiwen Cheng³, Yong Li⁴, Jiao Zhang⁵, Zhonghua Yang⁶, Li Li⁷, Haixia Zhou⁸, Suhong Li⁹, Huimin Xia¹, Yan Zou¹, Jing He¹, Tianyou Yang¹

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, China.
² Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin, China.
³ Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁴ Department of Pediatric Surgery, Hunan Children's Hospital, Changsha, China.
⁵ Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁶ Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
⁷ 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, China.
⁸ Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
⁹ Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan, China.

Abstract

Neuroblastoma is a primary malignancy mainly occurring in children. We have reported that polymorphisms of several N6-methyladenosine (m6A) RNA modification-related genes contributed to neuroblastoma risk in previous studies. YTHDF2, a "reader" of RNA m6A modification, is involved in cancer progression. Here, we estimated the association between a YTHDF2 gene rs3738067 A>G polymorphism and neuroblastoma susceptibility in 898 neuroblastoma patients and 1,734 healthy individuals from China. We found that the rs3738067 A>G could decrease neuroblastoma risk [AG vs. AA: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.64-0.90, P = 0.002; AG/GG vs. AA: adjusted OR = 0.81, 95% CI = 0.69-0.95, P = 0.011). Besides, the rs3738067 AG/GG genotype was related to reduced neuroblastoma risk in the following subgroups: children aged 18 months and under, boys, patients with tumors originating from retroperitoneal, patients at clinical stage IV, and cases at clinical stages III plus IV. Importantly, false-positive report probability analysis proved our significant results worthy of close attention of. The expression quantitative trait locus analysis results revealed that the rs3738067 was associated with the expression of YTHDF2.

Keywords: YTHDF2; neuroblastoma; polymorphism; rs3738067; susceptibility.