Cargando…

Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma

BACKGROUND: The enhancer of zeste 2 (EZH2) gene encodes the histone methyltransferase that is the catalytic component of the polycomb repressive complex-2, which initiates epigenetic silencing of genes. The expression level of EZH2 in hepatocellular carcinoma (HCC) is highly correlated with tumor pr...

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Yung-Luen, Su, Kuo-Jung, Hsieh, Yi-Hsien, Lee, Hsiang-Lin, Chen, Tzy-Yen, Hsiao, Pei-Ching, Yang, Shun-Fa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769270/
https://www.ncbi.nlm.nih.gov/pubmed/24040354
http://dx.doi.org/10.1371/journal.pone.0074870
_version_ 1782283956146667520
author Yu, Yung-Luen
Su, Kuo-Jung
Hsieh, Yi-Hsien
Lee, Hsiang-Lin
Chen, Tzy-Yen
Hsiao, Pei-Ching
Yang, Shun-Fa
author_facet Yu, Yung-Luen
Su, Kuo-Jung
Hsieh, Yi-Hsien
Lee, Hsiang-Lin
Chen, Tzy-Yen
Hsiao, Pei-Ching
Yang, Shun-Fa
author_sort Yu, Yung-Luen
collection PubMed
description BACKGROUND: The enhancer of zeste 2 (EZH2) gene encodes the histone methyltransferase that is the catalytic component of the polycomb repressive complex-2, which initiates epigenetic silencing of genes. The expression level of EZH2 in hepatocellular carcinoma (HCC) is highly correlated with tumor progression; however, it has not been determined if specific EZH2 genetic variants are associated with the risk of HCC. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with HCC susceptibility and its clinicopathologic characteristics. METHODOLOGY/PRINCIPAL FINDINGS: A total of 220 HCC patients and 552 cancer-free controls were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, the individuals carrying at least one C allele at EZH2 rs6950683 and rs3757441 had a 0.611-fold and a 0.660-fold lower risk of developing HCC than did wild-type (TT) carriers, respectively. The CCCA or CCTA haplotype among the four EZH2 sites (rs6950683, rs2302427, rs3757441, and rs41277434), respectively, was also associated with a reduced risk of HCC. Furthermore, HCC patients who carried at least one C allele at rs6950683 or rs3757441 had a higher lymph–node-metastasis risk but a lower liver-cirrhosis risk than did patients carrying the wild-type allele. CONCLUSIONS: The rs6950683 and rs3757441 polymorphic genotypes of EZH2 might contribute to the prediction of susceptibility to and pathological development of HCC. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of HCC in Taiwan.
format Online
Article
Text
id pubmed-3769270
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37692702013-09-13 Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma Yu, Yung-Luen Su, Kuo-Jung Hsieh, Yi-Hsien Lee, Hsiang-Lin Chen, Tzy-Yen Hsiao, Pei-Ching Yang, Shun-Fa PLoS One Research Article BACKGROUND: The enhancer of zeste 2 (EZH2) gene encodes the histone methyltransferase that is the catalytic component of the polycomb repressive complex-2, which initiates epigenetic silencing of genes. The expression level of EZH2 in hepatocellular carcinoma (HCC) is highly correlated with tumor progression; however, it has not been determined if specific EZH2 genetic variants are associated with the risk of HCC. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with HCC susceptibility and its clinicopathologic characteristics. METHODOLOGY/PRINCIPAL FINDINGS: A total of 220 HCC patients and 552 cancer-free controls were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, the individuals carrying at least one C allele at EZH2 rs6950683 and rs3757441 had a 0.611-fold and a 0.660-fold lower risk of developing HCC than did wild-type (TT) carriers, respectively. The CCCA or CCTA haplotype among the four EZH2 sites (rs6950683, rs2302427, rs3757441, and rs41277434), respectively, was also associated with a reduced risk of HCC. Furthermore, HCC patients who carried at least one C allele at rs6950683 or rs3757441 had a higher lymph–node-metastasis risk but a lower liver-cirrhosis risk than did patients carrying the wild-type allele. CONCLUSIONS: The rs6950683 and rs3757441 polymorphic genotypes of EZH2 might contribute to the prediction of susceptibility to and pathological development of HCC. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of HCC in Taiwan. Public Library of Science 2013-09-10 /pmc/articles/PMC3769270/ /pubmed/24040354 http://dx.doi.org/10.1371/journal.pone.0074870 Text en © 2013 Yu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yu, Yung-Luen
Su, Kuo-Jung
Hsieh, Yi-Hsien
Lee, Hsiang-Lin
Chen, Tzy-Yen
Hsiao, Pei-Ching
Yang, Shun-Fa
Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma
title Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma
title_full Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma
title_fullStr Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma
title_full_unstemmed Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma
title_short Effects of EZH2 Polymorphisms on Susceptibility to and Pathological Development of Hepatocellular Carcinoma
title_sort effects of ezh2 polymorphisms on susceptibility to and pathological development of hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769270/
https://www.ncbi.nlm.nih.gov/pubmed/24040354
http://dx.doi.org/10.1371/journal.pone.0074870
work_keys_str_mv AT yuyungluen effectsofezh2polymorphismsonsusceptibilitytoandpathologicaldevelopmentofhepatocellularcarcinoma
AT sukuojung effectsofezh2polymorphismsonsusceptibilitytoandpathologicaldevelopmentofhepatocellularcarcinoma
AT hsiehyihsien effectsofezh2polymorphismsonsusceptibilitytoandpathologicaldevelopmentofhepatocellularcarcinoma
AT leehsianglin effectsofezh2polymorphismsonsusceptibilitytoandpathologicaldevelopmentofhepatocellularcarcinoma
AT chentzyyen effectsofezh2polymorphismsonsusceptibilitytoandpathologicaldevelopmentofhepatocellularcarcinoma
AT hsiaopeiching effectsofezh2polymorphismsonsusceptibilitytoandpathologicaldevelopmentofhepatocellularcarcinoma
AT yangshunfa effectsofezh2polymorphismsonsusceptibilitytoandpathologicaldevelopmentofhepatocellularcarcinoma