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H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study
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 mal...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077085/ https://www.ncbi.nlm.nih.gov/pubmed/33403826 http://dx.doi.org/10.1002/mgg3.1584 |
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author | Li, Wenya Hua, Rui‐Xi Wang, Mi Zhang, Da Zhu, Jinhong Zhang, Songyang Yang, Yang Cheng, Jiwen Zhou, Haixia Zhang, Jiao He, Jing |
author_facet | Li, Wenya Hua, Rui‐Xi Wang, Mi Zhang, Da Zhu, Jinhong Zhang, Songyang Yang, Yang Cheng, Jiwen Zhou, Haixia Zhang, Jiao He, Jing |
author_sort | Li, Wenya |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8077085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80770852021-04-29 H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study Li, Wenya Hua, Rui‐Xi Wang, Mi Zhang, Da Zhu, Jinhong Zhang, Songyang Yang, Yang Cheng, Jiwen Zhou, Haixia Zhang, Jiao He, Jing Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2021-01-05 /pmc/articles/PMC8077085/ /pubmed/33403826 http://dx.doi.org/10.1002/mgg3.1584 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Li, Wenya Hua, Rui‐Xi Wang, Mi Zhang, Da Zhu, Jinhong Zhang, Songyang Yang, Yang Cheng, Jiwen Zhou, Haixia Zhang, Jiao He, Jing H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study |
title |
H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study |
title_full |
H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study |
title_fullStr |
H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study |
title_full_unstemmed |
H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study |
title_short |
H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study |
title_sort | h19 gene polymorphisms and wilms tumor risk in chinese children: a four‐center case‐control study |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077085/ https://www.ncbi.nlm.nih.gov/pubmed/33403826 http://dx.doi.org/10.1002/mgg3.1584 |
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