H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four-center case-control study

Wenya Li; Rui-Xi Hua; Mi Wang; Da Zhang; Jinhong Zhu; Songyang Zhang; Yang Yang; Jiwen Cheng; Haixia Zhou; Jiao Zhang; Jing He

doi:10.1002/mgg3.1584

H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four-center case-control study

Mol Genet Genomic Med. 2021 Feb;9(2):e1584. doi: 10.1002/mgg3.1584. Epub 2021 Jan 5.

Authors

Wenya Li¹, Rui-Xi Hua^{2

3}, Mi Wang³, Da Zhang¹, Jinhong Zhu^{3

4}, Songyang Zhang¹, Yang Yang¹, Jiwen Cheng⁵, Haixia Zhou⁶, Jiao Zhang¹, Jing He³

Affiliations

¹ Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 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, China.
⁴ Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin, China.
⁵ Department of Pediatric Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁶ Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Background: Wilms tumor is the most common pediatric renal cancer. However, genetic bases behind Wilms tumor remain largely unknown. H19 is a critical maternally imprinted gene. Previous studies indicated that single nucleotide polymorphisms (SNPs) in the H19 can modify the risk of several human malignancies. Epigenetic errors at the H19 locus lead to biallelic silencing in Wilms tumors. Genetic variations in the H19 may be related to Wilms tumor susceptibility.

Methods: We conducted a four-center study to investigate whether H19 SNP was a predisposing factor to Wilms tumor. Three polymorphisms in the H19 (rs2839698 G > A, rs3024270 C > G, rs217727 G > A) were genotyped in 355 cases and 1070 cancer-free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.

Results: We found that all of these three polymorphisms were significantly associated with Wilms tumor risk alterations. The rs2839698 G > A polymorphism (AG vs. GG: adjusted OR = 0.74, 95% CI = 0.57-0.96, p = 0.024; AA vs. GG: adjusted OR = 1.52, 95% CI = 1.05-2.22, p = 0.027), the rs3024270 C > G polymorphism (CG vs. CC: adjusted OR = 0.61, 95% CI = 0.46-0.81, p = 0.0007; and the rs217727 polymorphism (AG vs. GG: adjusted OR = 0.76, 95% CI = 0.58-0.99, p = 0.035). The Carriers of 1, 2, and 1-2 risk genotypes were inclined to develop Wilms tumor compared with those without risk genotype (adjusted OR = 1.36, 95% CI = 1.02-1.80, p = 0.037; adjusted OR = 1.84, 95% CI = 1.27-2.67, p = 0.001; adjusted OR = 1.50, 95% CI = 1.17-1.92, p = 0.002, respectively). The stratified analysis further revealed that rs2839698 AA, rs217727 AA, and 1-2 risk genotypes could strongly increase Wilms tumor risk among children above 18 months of age, males, and with clinical stage I+II disease.

Conclusion: Our findings indicate that genetic variations in the H19 may confer Wilms tumor risk.

Keywords: H19; Wilms tumor; polymorphism; susceptibility.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Child, Preschool
China
Female
Genes, Modifier
Humans
Infant
Male
Polymorphism, Single Nucleotide*
RNA, Long Noncoding / genetics*
Wilms Tumor / genetics*

Substances

H19 long non-coding RNA
RNA, Long Noncoding