J Cancer 2022; 13(12):3342-3347. doi:10.7150/jca.76255 This issue

Research Paper

WDR4 gene polymorphisms increase hepatoblastoma susceptibility in girls

Shaohua He1#, Jinhong Zhu2#, Zhixiang Xiao1#, Jiabin Liu3, Jiao Zhang4, Yong Li5, Zhonghua Yang6, Jiwen Cheng7, Suhong Li8, Li Li9, Jing He3✉, Di Xu1✉

1. Department of Pediatric Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, Fujian, China.
2. Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, 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.
4. Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
5. Department of Pediatric Surgery, Hunan Children's Hospital, Changsha 410004, Hunan, China.
6. Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
7. Department of Pediatric Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.
8. Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China.
9. 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.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
He S, Zhu J, Xiao Z, Liu J, Zhang J, Li Y, Yang Z, Cheng J, Li S, Li L, He J, Xu D. WDR4 gene polymorphisms increase hepatoblastoma susceptibility in girls. J Cancer 2022; 13(12):3342-3347. doi:10.7150/jca.76255. Available from https://www.jcancer.org/v13p3342.htm

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Graphic abstract

Hepatoblastoma, originating from hepatoblasts, is the most common hepatic malignancy. WD repeat domain 4 (WDR4) is a subunit of RNA N(7)-methylguanine (m7G) methyltransferase complex. Recently, WDR4 has shown oncogenic potential in various adult cancers, but its roles in pediatric cancers have not been reported. We performed a case-control study (313 cases vs. 1446 controls) to investigate whether genetic variants in the WDR4 gene influence hepatoblastoma susceptibility in the Chinese Han nationality. We first determine the genotypes of five WDR4 gene polymorphisms (rs2156315 C>T, rs2156316 C>G, rs6586250 C>T, rs15736 G>A, rs2248490 C>G) in participants, using the Taqman assay. And then, an unconditional logistic regression analysis was performed to assess the association between WDR4 gene polymorphisms and hepatoblastoma risk. Overall, we did not find any polymorphism significantly associated with the risk of developing hepatoblastoma. Instead, the stratified analysis revealed that the co-existence of 2-5 risk genotypes increased hepatoblastoma risk by 2.23 folds in girls (adjusted odds ratio=2.23, 95% confidence interval=1.17-4.23, P=0.014). In conclusion, our results demonstrate that single selected polymorphisms were too weak to exert a significant effect on the whole study population. However, in combination, two or more WDR4 gene polymorphisms significantly conferred increased hepatoblastoma risk in girls. Our findings may encourage more genetic association studies to discover significant polymorphisms in the WDR4 gene for hepatoblastoma.

Keywords: hepatoblastoma, susceptibility, WDR4, polymorphism, m7G